Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 58
Filtrar
Más filtros











Intervalo de año de publicación
1.
Arq. bras. med. vet. zootec. (Online) ; 72(5): 1666-1674, Sept.-Oct. 2020. tab, ilus
Artículo en Portugués | LILACS, VETINDEX | ID: biblio-1131549

RESUMEN

O objetivo deste estudo foi avaliar as alterações cardiorrespiratórias causadas pela medetomidina associada à cetamina, e o tempo de recuperação após aplicação intramuscular de atipamezole ou ioimbina em Puma concolor. Para isso, foi realizada a aplicação de medetomidina (100µg/kg) associada à cetamina (5mg/kg) em 11 onças-pardas, sendo os parâmetros cardiorrespiratórios registrados a cada 15 minutos, durante 90 minutos de avaliação. Em seguida, a anestesia foi revertida com aplicação intramuscular de ioimbina (0,4mg/kg; n=5) ou atipamezole (0,25mg/kg; n=6), sendo analisado o tempo até a recuperação. Dos parâmetros cardiorrespiratórios avaliados, houve diferença apenas na frequência respiratória (entre os momentos 60 e 90 minutos), estando esta, todavia, dentro do intervalo de referência para a espécie. Além disso, verificou-se tempo para decúbito esternal significativamente menor nos animais do grupo atipamezole (18±7 minutos), quando comparado ao grupo ioimbina (36±17 minutos), entretanto o tempo de recuperação completa foi estatisticamente igual entre os dois reversores analisados. Assim, a associação anestésica promoveu anestesia eficiente, segura e de rápida indução em onças-pardas, permitindo a imobilização dos animais durante os 90 minutos de avaliação, sem a ocorrência de complicações. Ao se comparar a reversão anestésica com atipamezole e ioimbina, observou-se equivalência dos fármacos no tempo de recuperação completa dos animais.(AU)


The aim of this study was to evaluate the cardiorespiratory changes caused by ketamine-associated medetomidine, and the recovery time after intramuscular application of atipamezole or yohimbine in Puma concolor. For this, the application of medetomidine (100µg/kg) associated with ketamine (5mg/kg) was performed in eleven brown ounces, and the cardiorespiratory parameters were recorded every 15 minutes during 90 minutes of evaluation. Afterwards, anesthesia was reversed with intramuscular application of yohimbine (0.4mg/kg; n=5) or atipamezole (0.25mg/kg; n=6), and time to recovery was analyzed. Of the cardiorespiratory parameters evaluated, there was a difference only in respiratory rate (between 60 and 90 minutes), however, within the reference range for the species. In addition, there was a significantly shorter time for sternal decubitus in the animals of the atipamezole group (18±7 minutes) when compared to the yohimbine group (36±17 minutes), however the complete recovery time was statistically equal between the two reversers analyzed. Thus, the anesthetic association promoted efficient, safe and fast induction anesthesia in puma, allowing the animals to be immobilized during the 90 minutes of evaluation without complications. Comparing anesthetic reversal with atipamezole and yohimbine, drug equivalence was observed in the complete recovery time of the animals.(AU)


Asunto(s)
Animales , Yohimbina/uso terapéutico , Medetomidina/administración & dosificación , Puma/fisiología , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Antagonistas de Receptores Adrenérgicos alfa 2/análisis , Ketamina/administración & dosificación , Periodo de Recuperación de la Anestesia
2.
BMC Vet Res ; 16(1): 304, 2020 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-32831087

RESUMEN

BACKGROUND: Sterilization clinics often occur in remote places where anesthesia machines and compressed oxygen are unavailable. This study describes the use of total injectable anesthesia in dogs and cats presented for sterilization in a remote location. RESULTS: A total of 100 animals were sterilized; 26 female cats (CF), 22 male cats (CM), 28 female dogs (DF), and 24 male dogs (DM). CF were anesthetized with dexmedetomidine (20 mcg/kg), ketamine (8 mg/kg) and hydromorphone (0.1 mg/kg) IM. CM were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. Insufficient anesthesia in cats was treated with alfaxalone (1 mg/kg) IM. All cats were administered meloxicam at 0.3 mg/kg SQ. DF were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (7-10 mg/kg) and hydromorphone (0.1 mg/kg) IM. DM were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. All dogs had IV catheter and endotracheal tube placed. If SpO2 < 91%, ventilation was assisted with an Ambu bag. Insufficient anesthesia in dogs was treated with alfaxalone (1 mg/kg) IV. All dogs were administered meloxicam at 0.2 mg/kg SQ. Following surgery, atipamezole (0.05-0.1 mg/kg) IM was administered to any patient that did not have voluntary movement. All patients survived and were discharged. Less than 25% of cats and male dogs required supplemental anesthesia. Fifty seven percent of female dogs required supplemental anesthesia. More than 89% of patients (in any group) required atipamezole administration. One cat recovered with agitation and hyperthermia (41.1C/ 106F). Some dogs required ventilatory assistance to remain normoxemic while anesthetized. CONCLUSION: Total injectable anesthesia can be accomplished for remote location sterilization clinics with minimal morbidity.


Asunto(s)
Anestesia Intravenosa/veterinaria , Gatos/cirugía , Perros/cirugía , Orquiectomía/veterinaria , Ovariectomía/veterinaria , Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Anestésicos Combinados/administración & dosificación , Animales , Dexmedetomidina/administración & dosificación , Ecuador , Femenino , Hidromorfona/administración & dosificación , Imidazoles/administración & dosificación , Ketamina/administración & dosificación , Masculino , Meloxicam/administración & dosificación , Pregnanodionas
3.
J Wildl Dis ; 56(2): 447-451, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31750774

RESUMEN

A combination (mean±SD) of ketamine (4.0±1.0 mg/kg in juveniles and 3.0±0.4 in adults) and dexmedetomidine (0.055±0.01 and 0.049±0.01, respectively), reversed with atipamezole (at 10 mg/mg of dexmedetomidine), was assessed in 57 Andean foxes (Lycalopex culpaeus) in field conditions. Induction times in juveniles and adults were 4.6±3.9 min and 4.3±2.4 min, respectively. Immobilization was smooth and safe, and lasted 50±8 min in juveniles and 50±10 min in adults. Full recovery was recorded at 40±29 min in juveniles and 37±23 min in adults after atipamezole administration. Drug dose, season, body temperature, and fox sex and body condition were not related to variations in induction and recovery times, body temperature, heart rate, respiratory rate, or hemoglobin oxygen saturation. No side effects were observed other than a slight but significant decrease in mean body temperature during the procedure. This combination allowed carrying out all the typical procedures of a research project, including the collection of several biologic samples.


Asunto(s)
Dexmedetomidina/farmacología , Zorros , Imidazoles/farmacología , Inmovilización/veterinaria , Ketamina/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Anestésicos Disociativos/administración & dosificación , Anestésicos Disociativos/farmacología , Animales , Dexmedetomidina/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacología , Imidazoles/administración & dosificación , Ketamina/administración & dosificación
4.
J Med Primatol ; 48(6): 351-356, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31194266

RESUMEN

BACKGROUND: A smooth and rapid recovery from anesthesia allowing safe release is desirable, especially for wild species. This study describes the clinical effects of the combination of dexmedetomidine and ketamine and the partial reversal with atipamezole in golden-headed lion tamarins. METHODS: Dexmedetomidine 10 µg kg-1 and ketamine 15 mg kg-1 were administered to 45 golden-headed lion tamarins undergoing vasectomy. Following surgery, animals were assigned to three groups: control (SAL; 0.9% NaCl), atipamezole 20 µg kg-1 (ATI20), and atipamezole 40 µg kg-1 (ATI40). RESULTS AND CONCLUSIONS: All animals presented great scores of sedation and muscle relaxation during the procedure. Recovery in the control group was smooth and uneventful. Salivation, muscle tremors, and head movements were observed in ATI 20 and ATI40. The administration of atipamezole did not change total recovery times (ATI20 69 ± 23 minutes; ATI40 72 ± 45 minutes; SAL 57 ± 23 minutes).


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Dexmedetomidina/farmacología , Hipnóticos y Sedantes/farmacología , Imidazoles/farmacología , Ketamina/farmacología , Leontopithecus/fisiología , Animales , Relación Dosis-Respuesta a Droga , Masculino , Distribución Aleatoria , Vasectomía/veterinaria
5.
ACS Chem Neurosci ; 10(7): 3173-3182, 2019 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-30695640

RESUMEN

Calcitonin gene-related peptide (α-CGRP) released from perivascular sensory nerves induces decreases in diastolic blood pressure (DBP). Experimentally, this can be shown by spinal thoracic (T9-T12) electrical stimulation of these afferent fibers. Because ergotamine inhibits these neurogenic vascular responses and displays affinity for monoaminergic receptors that inhibit neurotransmitter release, we investigated whether this ergotamine-induced inhibition results from activation of serotonin 5-HT1B/1D, dopamine D2-like, and α2-adrenergic receptors. Wistar rats were pithed and, under autonomic ganglion blockade, received intravenous infusions of methoxamine followed by ergotamine (0.1-3.1 µg kg-1 min-1). Thoracic T9-T12 electrical stimulation or an intravenous bolus of α-CGRP resulted in decreases in DBP. Ergotamine inhibited the electrically induced, but not α-CGRP-induced, responses. The vasodilator sensory inhibition by 3.1 µg of ergotamine kg-1 min-1 was resistant to simultaneous blockade of 5-HT1B/1D, D2-like, and α2-adrenergic receptors upon addition of antagonists GR127935, haloperidol, and rauwolscine. Moreover, the inhibition by 0.31 µg of ergotamine kg-1 min-1 was unaltered by GR127935 and haloperidol, partly blocked by GR127935 and rauwolscine or rauwolscine and haloperidol, and abolished by GR127935, haloperidol, and rauwolscine. These findings imply that prejunctional 5-HT1B/1D, D2-like, and α2-adrenergic receptors mediate the sensory inhibition induced by 0.31 µg of ergotamine kg-1 min-1, whereas larger doses may involve other receptors. Thus, ergotamine's ability to inhibit the perivascular sensory peptidergic drive may result in facilitation of its systemic vasoconstrictor properties.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 1/farmacología , Sistema Nervioso Autónomo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Péptido Relacionado con Gen de Calcitonina/farmacología , Ergotamina/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Sistema Nervioso Autónomo/fisiología , Presión Sanguínea/fisiología , Antagonistas de Dopamina , Estimulación Eléctrica , Haloperidol/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Masculino , Oxadiazoles/farmacología , Piperazinas/farmacología , Ratas , Ratas Wistar , Antagonistas de la Serotonina , Yohimbina/farmacología
6.
Behav Brain Res ; 346: 86-95, 2018 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-29191577

RESUMEN

Cortical electrical stimulation (CES) has shown to be an effective therapeutic alternative for neuropathic pain refractory to pharmacological treatment. The primary motor cortex(M1) was the main cortical target used in the vast majority of both invasive and non-invasive studies. Despite positive results M1-based approaches still fail to relieve pain in a significant proportion of individuals. It has been advocated that the direct stimulation of cortical areas directly implicated in the central integration of pain could increase the efficacy of analgesic brain stimulation. Here, we evaluated the behavioral effects of electrical stimulation of the insular cortex (ESI) on pain sensitivity in an experimental rat model of peripheral neuropathy, and have described the pathways involved. Animals underwent chronic constriction of the sciatic nerve in the right hind limb and had concentric electrodes implanted in the posterior dysranular insular cortex. Mechanical nociception responses were evaluated before and at the end of a 15-min session of ESI (60Hz, 210µs, 1V). ESI reversed mechanical hypersensitivity in the paw contralateral to the brain hemisphere stimulated, without inducing motor impairment in the open-field test. Pharmacological blockade of µ-opioid (MOR) or type 1-cannabinoid receptors (CB1R) abolished ESI-induced antinociceptive effects. Evaluation of CB1R and MOR spatial expression demonstrated differential modulation of CB1R and MOR in the periaqueductal gray matter (PAG) of ESI-treated rats in sub-areas involved in pain processing/modulation. These results indicate that ESI induces antinociception by functionally modulating opioid and cannabinoid systems in the PAG pain circuitry in rats with experimentally induced neuropathic pain.


Asunto(s)
Corteza Cerebral/fisiopatología , Dolor Crónico/fisiopatología , Dolor Crónico/terapia , Estimulación Encefálica Profunda , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/terapia , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Corteza Cerebral/efectos de los fármacos , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Masculino , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Dolor Nociceptivo/fisiopatología , Dolor Nociceptivo/terapia , Sustancia Gris Periacueductal/efectos de los fármacos , Sustancia Gris Periacueductal/metabolismo , Distribución Aleatoria , Ratas Sprague-Dawley , Receptor Cannabinoide CB1/antagonistas & inhibidores , Receptor Cannabinoide CB1/metabolismo , Receptores Opioides mu/antagonistas & inhibidores , Receptores Opioides mu/metabolismo , Antagonistas de la Serotonina/farmacología , Tacto
7.
Int Immunopharmacol ; 38: 402-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27355133

RESUMEN

Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1ß by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time.


Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Eugenol/uso terapéutico , Leucocitos/efectos de los fármacos , Actividad Motora , Dolor/tratamiento farmacológico , Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Animales , Permeabilidad Capilar/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Eugenol/química , Calor/efectos adversos , Interleucina-1beta/metabolismo , Leucocitos/fisiología , Masculino , Ratones , Actividad Motora/efectos de los fármacos , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Yohimbina/administración & dosificación , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
9.
Int J Neuropsychopharmacol ; 18(1)2014 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-25539509

RESUMEN

BACKGROUND: Traumatic memories have been resilient to therapeutic approaches targeting their permanent attenuation. One of the potentially promising pharmacological strategies under investigation is the search for safe reconsolidation blockers. However, preclinical studies focusing on this matter have scarcely addressed abnormal aversive memories and related outcomes. METHODS: By mimicking the enhanced noradrenergic activity reported after traumatic events in humans, here we sought to generate a suitable condition to establish whether some clinically approved drugs able to disrupt the reconsolidation of conditioned fear memories in rodents would still be effective. RESULTS: We report that the α2-adrenoceptor antagonist yohimbine was able to induce an inability to restrict behavioral (fear) and cardiovascular (increased systolic blood pressure) responses to the paired context when administered immediately after acquisition, but not 6h later, indicating the formation of a generalized fear memory, which endured for over 29 days and was less susceptible to suppression by extinction. It was also resistant to reconsolidation disruption by the α2-adrenoceptor agonist clonidine or cannabidiol, the major non-psychotomimetic component of Cannabis sativa. Since signaling at N-methyl-D-aspartate (NMDA) receptors is important for memory labilization and because a dysfunctional memory may be less labile than is necessary to trigger reconsolidation on its brief retrieval and reactivation, we then investigated and demonstrated that pre-retrieval administration of the partial NMDA agonist D-cycloserine allowed the disrupting effects of clonidine and cannabidiol on reconsolidation. CONCLUSIONS: These findings highlight the effectiveness of a dual-step pharmacological intervention to mitigate an aberrant and enduring aversive memory similar to that underlying the post-traumatic stress disorder.


Asunto(s)
Miedo/efectos de los fármacos , Memoria/efectos de los fármacos , Psicotrópicos/farmacología , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Cannabidiol/farmacología , Clonidina/farmacología , Cicloserina/farmacología , Fármacos actuantes sobre Aminoácidos Excitadores/farmacología , Extinción Psicológica/efectos de los fármacos , Miedo/fisiología , Masculino , Distribución Aleatoria , Ratas Wistar , Trastornos por Estrés Postraumático/tratamiento farmacológico , Yohimbina/farmacología
10.
BMC Vet Res ; 10: 170, 2014 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-25103781

RESUMEN

BACKGROUND: Alpha adrenergic drugs are usually used in the treatment of erectile and ejaculatory dysfunction in humans. The influence of such drugs on the seminal characteristics of wild animals has not been verified; whereas their impact on the seminal characteristics and erectile and ejaculatory functions of collared peccaries (Tayassu tajacu) has already been determined. This study aimed at investigating and comparing the effects of medetomidine and atipamezole on the seminal variables of collared peccaries undergoing electroejaculation as well as at determining whether these drugs affected the erectile and ejaculatory functions of this species. RESULTS: A statistically significant difference in sperm concentration was observed between AP (100.0 ± 26.0 × 106 sperm/ml) and MP (220.2 ± 49.8 × 106 sperm/ml); however, both these treatments did not differ from P treatment (180.0 ± 50.7 × 106 sperm/ml). No statistically significant difference was observed among all treatments with regard to erectile function. With regard to ejaculation time, no significant difference was observed between the MP and AP treatments; however, when compared with the P treatment, AP exhibited a significantly higher difference. CONCLUSIONS: When collared peccaries were anesthetized with propofol, neither medetomidine nor atipamezole significantly affected the characteristics of the semen or the erectile function, despite the fact that the AP treatment increased ejaculation time. Therefore, the data indicate that using propofol alone is an effective anesthetic protocol for collecting semen in collared peccaries. Other non-injectable anesthetic drugs, such as inhaled anesthetics, may be used in future research to collect semen from peccaries.


Asunto(s)
Artiodáctilos/fisiología , Eyaculación/efectos de los fármacos , Imidazoles/farmacología , Medetomidina/farmacología , Erección Peniana/efectos de los fármacos , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Estudios Cruzados , Estimulación Eléctrica , Masculino , Análisis de Semen/veterinaria , Recuento de Espermatozoides/veterinaria
11.
J Ethnopharmacol ; 155(3): 1616-24, 2014 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-25153020

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Celtis iguanaea (Canabaceae) is popularly known as esporão-de-galo, stands out among the medicinal plants used for treatment of gastric ulcers. In Brazil, the leaves they are used traditionally in infusion forms as an analgesic, antiasthmatic, digestive and diuretic. AIM OF THE STUDY: The present study was aimed to investigate the antiulcer mechanisms of hexane extract Celtis iguanaea leaves (HE) in several induced-gastric ulcer and characterize its chemical composition. MATERIALS AND METHODS: The HE was obtained by exhaustive extraction in Soxhlet apparatus. The chemical characterization of HE was performed by Electrospray Fourier transform ion cyclotron mass spectrometry (ESI FT-ICR MS) analysis. Mice were used for the evaluation of the gastroprotective activity. HE was analyzed in the HCl/ethanol, hypothermic restraint stress ulcer and acetic acid. In the investigation of the gastroprotective mechanisms of HE, were performed the amount of adhered gastric mucus, participation of the α2-adrenoceptor, nitric oxide (NO) and prostaglandins (PGs) using the HCl/ethanol-induced gastric mucosa lesion model. RESULTS: ESI FT-ICR MS analysis of HE suggest the presence of compounds as lipids, sterol lipids, steroids glycosides and polyphenol glycosides. The oral administration of HE at doses of 100 mg/kg or 200 mg/kg was able to protect the gastric mucosa against HCl/ethanol (10 mL/kg p.o.), and HE at dose of 100mg/kg protected against hypothermic-restraint stress and acetic -induced gastric lesions. The pretreatment with Yoimbine (2mg/kg, s.c.), an antagonist α2-adrenergic, L-NAME (20mg/kg, s.c.), an inhibitor of nitric oxide synthesis or indomethacin (10mg/kg, s.c.), an inhibitor of prostaglandin production, reversed the gastroprotective activity of HE (100mg/kg, p.o.). CONCLUSIONS: Our results suggest that the Celtis iguanaea HE exhibits gastroprotective activity in different gastric ulcer models. The mechanism of gastroprotective effect of Celtis iguanaea HE suggests the participation of mucus as well as the involvement of α2-adrenergic receptors, NO and prostaglandins. The hydroxyl-linolenic acid, linoleic acids and conjugated oxo-linoleic acids are among the phytoconstituents that were identified in the Celtis iguanaea HE.


Asunto(s)
Antiulcerosos/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Ulmaceae , Ácido Acético , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Antiulcerosos/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Etanol , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Ácido Clorhídrico , Indometacina/farmacología , Masculino , Ratones , Moco/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Hojas de la Planta , Úlcera Gástrica/etiología , Úlcera Gástrica/patología , Estrés Fisiológico , Yohimbina/farmacología
12.
Mol Cell Biochem ; 388(1-2): 135-47, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24287564

RESUMEN

Citrus aurantium extracts, which contain large amounts of p-synephrine, are widely used for weight loss purposes and as appetite suppressants. In the liver, C. aurantium (bitter orange) extracts affect hemodynamics, carbohydrate metabolism, and oxygen uptake. The purpose of the present work was to quantify the action of p-synephrine and also to obtain indications about its mechanism of action, a task that would be difficult to accomplish with C. aurantium extracts due to their rather complex composition. The experimental system was the isolated perfused rat liver. p-Synephrine significantly stimulated glycogenolysis, glycolysis, gluconeogenesis, and oxygen uptake. The compound also increased the portal perfusion pressure and the redox state of the cytosolic NAD(+)/NADH couple. A Ca(2+)-dependency for both the hemodynamic and the metabolic effects of p-synephrine was found. p-Synephrine stimulated both cAMP overflow and the initial Ca(2+) release from the cellular stores previously labeled with (45)Ca(2+). The metabolic and hemodynamic actions of p-synephrine were strongly inhibited by α-adrenergic antagonists and moderately affected by ß-adrenergic antagonists. The results allow to conclude that p-synephrine presents important metabolic and hemodynamic effects in the liver. These effects can be considered as both catabolic (glycogenolysis) and anabolic (gluconeogenesis), they are mediated by both α- and ß-adrenergic signaling, require the simultaneous participation of both Ca(2+) and cAMP, and could be contributing to the overall stimulation of metabolism that usually occurs during weight loss periods.


Asunto(s)
Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Hígado/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Sinefrina/farmacología , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Antagonistas de Receptores Adrenérgicos beta 3/farmacología , Animales , Calcio/metabolismo , Citrus/metabolismo , AMP Cíclico/biosíntesis , Gluconeogénesis/efectos de los fármacos , Glucogenólisis/efectos de los fármacos , Glucólisis/efectos de los fármacos , Masculino , Oxidación-Reducción/efectos de los fármacos , Extractos Vegetales/farmacología , Prazosina/farmacología , Propanolaminas/farmacología , Propranolol/farmacología , Ácido Pirúvico/metabolismo , Ratas , Ratas Wistar , Transducción de Señal , Yohimbina/farmacología
13.
Neuropharmacology ; 73: 261-73, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23791558

RESUMEN

Pyrazole compounds are an intriguing class of compounds with potential analgesic activity; however, their mechanism of action remains unknown. Thus, the goal of this study was to explore the antinociceptive potential, safety and mechanism of action of novel 1-pyrazole methyl ester derivatives, which were designed by molecular simplification, using in vivo and in vitro methods in mice. First, tree 1-pyrazole methyl ester derivatives (DMPE, MPFE, and MPCIE) were tested in the capsaicin test and all presented antinociceptive effect; however the MPClE (methyl 5-trichloromethyl-3-methyl-1H-pyrazole-1-carboxylate) was the most effective. Thus, we selected this compound to assess the effects and mechanisms in subsequent pain models. MPCIE produced antinociception when administered by oral, intraperitoneal, intrathecal and intraplantar routes and was effective in the capsaicin and the acetic acid-induced nociception tests. Moreover, this compound reduced the hyperalgesia in diverse clinically-relevant pain models, including postoperative, inflammatory, and neuropathic nociception in mice. The antinociception produced by orally administered MPClE was mediated by κ-opioid receptors, since these effects were prevented by systemically pre-treatment with naloxone and the κ-opioid receptor antagonist nor-binaltorphimine. Moreover, MPCIE prevented binding of the κ-opioid ligand [(3)H]-CI-977 in vitro (IC50 of 0.68 (0.32-1.4) µM), but not the TRPV1 ([(3)H]-resiniferatoxin) or the α2-adrenoreceptor ([(3)H]-idazoxan) binding. Regarding the drug-induced side effects, oral administration of MPClE did not produce sedation, constipation or motor impairment at its active dose. In addition, MPCIE was readily absorbed after oral administration. Taken together, these results demonstrate that MPClE is a novel, potent, orally active and safe analgesic drug that targets κ-opioid receptors.


Asunto(s)
Analgésicos/farmacología , Pirazoles/farmacología , Receptores Opioides kappa/agonistas , Antagonistas de Receptores Adrenérgicos alfa 2 , Analgésicos/administración & dosificación , Analgésicos/antagonistas & inhibidores , Analgésicos/química , Animales , Benzofuranos , Diterpenos , Vías de Administración de Medicamentos , Evaluación Preclínica de Medicamentos , Idazoxan , Masculino , Ratones , Estructura Molecular , Naloxona/farmacología , Naltrexona/análogos & derivados , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Dimensión del Dolor , Pirazoles/administración & dosificación , Pirazoles/antagonistas & inhibidores , Pirazoles/química , Pirrolidinas , Ensayo de Unión Radioligante , Receptores Opioides kappa/antagonistas & inhibidores , Canales Catiónicos TRPV/efectos de los fármacos , Tritio
14.
Behav Brain Res ; 246: 76-85, 2013 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-23470900

RESUMEN

Exposure of rodents to an open elevated plus-maze (oEPM) elicits antinociception and increases plasma corticosterone levels. However, no studies have yet assessed the defensive behaviour repertoire of animals in this modified test. In Experiment 1, factor analysis was employed to characterise the behavioural profile of mice exposed to the oEPM. Experiments 2 and 3 assessed the effects of acute alprazolam (0.5-1.5mg/kg; diazepam 0.5-1.5mg/kg), pentylenetetrazole (10.0-30.0mg/kg), yohimbine (2.0-6.0mg/kg), mCPP (0.3-3.0mg/kg), and acute and chronic fluoxetine (10.0-30.0mg/kg) and imipramine (1.0-15.0mg/kg) on behaviours identified in Experiment 1. The factor analyses revealed that behaviour in the oEPM can largely (77% total variance) be accounted for in terms of 3 factors: factor 1 ('depth exploration'; e.g. head-dipping on the arms), factor 2 ('cautious exploration of arms'; e.g. flatback approach), and factor 3 ('risk assessment'; stretched attend postures - SAP). Experiments 2 and 3 showed that, over the dose range used, alprazolam selectively attenuated all measures of defensiveness. Similar, though more modest, effects were seen with diazepam. Confirming the intensity of the emotional response to the oEPM (nociceptive, endocrine and behavioural), relatively few significant behavioural changes were seen in response to the anxiogenic compounds tested. Although acute fluoxetine or imipramine treatment failed to modify behaviour in the oEPM, chronic fluoxetine (but not chronic imipramine) attenuated total flat back approach and increased head dipping outside the central square. Together, the results indicate that the oEPM induces behavioural defensive responses that are sensitive to alprazolam and chronic fluoxetine.


Asunto(s)
Alprazolam/farmacología , Ansiolíticos/farmacología , Antidepresivos de Segunda Generación/farmacología , Fluoxetina/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Convulsivantes/farmacología , Corticosterona/sangre , Diazepam/farmacología , Análisis Factorial , Masculino , Ratones , Pentilenotetrazol/farmacología , Estadísticas no Paramétricas , Yohimbina/farmacología
15.
Cir Cir ; 81(1): 28-32, 2013.
Artículo en Español | MEDLINE | ID: mdl-23461918

RESUMEN

INTRODUCTION: It has been proposed that noradrenaline is one of the neurotransmitters involved in the functional recovery. In this sense, it has been proposed that the alpha-2 noradrenergic receptors play an important role in the functional reinstatement. OBJECTIVE: the aim of this work was to study the role of the alpha-2 noradrenergic receptors on the noradrenaline contents in cerebellum and pons of rats iron-injured in the motor cortex. METHODS: Fifteen male Wistar rats were allocated in three groups: control (n = 5) with intracortical infusion of saline (0.9%), injured (n = 5) with intracortical infusion of dextran iron and intraventricular infusion of saline, and injured + yohimbine (alpha-2 receptor antagonist; n = 5) that received an intracortical infusion of dextran iron and also an intraventricular infusion of yohimbine. Motor behavior was assessed by means of the beam-walking paradigm. Three days after surgeries, the animals were sacrificed and the left and right sides of the pons and the cerebellar hemispheres were extracted. Tissues were prepared for noradrenaline analysis by means of high performance liquid chromatography. RESULTS: We observed that the yohimbine-treated animals had a noradrenaline increase in the right side of the pons and a decrease in the right cerebellar hemisphere. CONCLUSION: It is concluded that the blockage of the alpha-2 receptors leads to an increase of noradrenaline in the locus coeruleus, which retards the effects of the cerebral injury.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Lesiones Encefálicas/fisiopatología , Corteza Motora/efectos de los fármacos , Corteza Motora/fisiopatología , Desempeño Psicomotor/efectos de los fármacos , Receptores Adrenérgicos/efectos de los fármacos , Yohimbina/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Animales , Infusiones Intraventriculares , Masculino , Ratas , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Yohimbina/administración & dosificación
16.
Anesth Analg ; 116(3): 703-11, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23400995

RESUMEN

BACKGROUND: Several studies have demonstrated antinociception induced by exercise; however, the specific mechanisms for this effect are not well understood. Thus, we investigated the involvement of α2-adrenergic receptors (α2-ARs) in the antinociceptive effect produced by exercise in rats and mice. METHODS: Male Wistar rats performed acute aerobic (AA) and acute resistance exercise protocols, and male α2A/α2C-ARs knockout mice and their wild-type mice were also submitted to AA. RESULTS: After the exercise protocols, the nociceptive threshold of rats and wild type was increased, (except in knockout mice). This effect was reversed by yohimbine, a nonselective α2-ARs antagonist (4 mg/kg, subcutaneously [s.c.]); rauwolscine, a selective α2C-ARs antagonist (4 mg/kg, s.c.); BRL 44408, a selective α2A-ARs antagonist (4 mg/kg, s.c.) and guanethidine, a selective inhibitor of transmission in adrenergic nerves (30 mg/kg, intraperitoneal). Furthermore, when given intrathecally or intracerebroventricularly, yohimbine did not alter antinociception induced by exercise protocols. In addition, α2-ARs expression in rat brains did not change after AA and acute resistance exercise. CONCLUSION: These results suggest a peripheral involvement of α2-ARs in the antinociception induced by aerobic and resistance exercise.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Dimensión del Dolor/métodos , Condicionamiento Físico Animal/métodos , Condicionamiento Físico Animal/fisiología , Receptores Adrenérgicos alfa 2/fisiología , Entrenamiento de Fuerza/métodos , Animales , Inyecciones Intraventriculares , Inyecciones Espinales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Dimensión del Dolor/efectos de los fármacos , Ratas , Ratas Wistar
17.
Inflammation ; 36(3): 705-12, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23377962

RESUMEN

In the present study, the antinociceptive profile of oligopeptidases B from Trypanosoma cruzi (OPTc) and Trypanosoma brucei (OPTb) were examined in mice evaluated by the acetic acid-induced writhing test. Both OPTc and OPTb injected intraperitoneally attenuated the writhing numbers in the acetic acid-induced writhing test. This effect was not dependent on the enzymatic activity, but the enzyme structure was important for this purpose. Intraperitoneal pretreatment with methysergide (5-HT serotonergic receptor antagonist) attenuated antinociceptive effect induced by both OPTc and OPTb in the writhing test. However, naloxone (opioid receptor antagonist) or yohimbine (α2-adrenergic receptor antagonist) did not affect antinociception induced by both oligopeptidases. Our results suggest that OPTc and OPTb show antinociceptive property in the writhing test. Furthermore, this antinociceptive effect may be mediated by serotonergic receptor but not opioidergic or α2-adrenergic receptors.


Asunto(s)
Analgésicos/farmacología , Dolor/tratamiento farmacológico , Receptores de Serotonina/metabolismo , Serina Endopeptidasas/farmacología , Trypanosoma brucei brucei/enzimología , Trypanosoma cruzi/enzimología , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Analgésicos/administración & dosificación , Analgésicos/uso terapéutico , Animales , Masculino , Metisergida , Ratones , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Dimensión del Dolor/efectos de los fármacos , Serina Endopeptidasas/administración & dosificación , Antagonistas de la Serotonina/farmacología , Trypanosoma brucei brucei/metabolismo , Yohimbina/farmacología
18.
Anesth Analg ; 116(2): 463-72, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23302980

RESUMEN

BACKGROUND: Cannabinoid agonists induce norepinephrine release in central, spinal, and peripheral sites. Previous studies suggest an interaction between the cannabinoid and adrenergic systems on antinociception. In this study, we sought to verify whether the CB1 and CB2 cannabinoid receptor agonists anandamide and N-palmitoyl-ethanolamine (PEA), respectively, are able to induce peripheral antinociception via an adrenergic mechanism. METHODS: All drugs were administered locally into the right hindpaw of male Wistar rats. The rat paw pressure test was used, with hyperalgesia induced by intraplantar injection of prostaglandin E2 (2 µg). RESULTS: Anandamide, 12.5 ng/paw, 25 ng/paw, and 50 ng/paw elicited a local peripheral antinociceptive effect that was antagonized by CB1 cannabinoid receptor antagonist AM251, 20 µg/paw, 40 µg/paw, and 80 µg/paw, but not by CB2 cannabinoid receptor antagonist AM630, 100 µg/paw. PEA, 5 µg/paw, 10 µg/paw, and 20 µg/paw, elicited a local peripheral antinociceptive effect that was antagonized by AM630, 25 µg/paw, 50 µg/paw, and 100 µg/paw, but not by AM251, 80 µg/paw. Antinociception induced by anandamide or PEA was antagonized by the nonselective α2 adrenoceptor antagonist yohimbine, 05 µg/paw, 10 µg/paw, and 20 µg/paw, and by the selective α2C adrenoceptor antagonist rauwolscine, 10 µg/paw, 15 µg/paw, and 20 µg/paw, but not by the selective antagonists for α2A, α2B, and α2D adrenoceptor subtypes, 20 µg/paw. The antinociceptive effect of the cannabinoids was also antagonized by the nonselective α1 adrenoceptor antagonist prazosin, 0.5 µg/paw, 1 µg/paw, and 2 µg/paw, and by the nonselective ß adrenoceptor antagonist propranolol, 150 ng/paw, 300 ng/paw, and 600 ng/paw. Guanethidine, which depletes peripheral sympathomimetic amines (30 mg/kg/animal, once a day for 3 days), restored approximately 70% the anandamide-induced and PEA-induced peripheral antinociception. Furthermore, acute injection of the norepinephrine reuptake inhibitor reboxetine, 30 µg/paw, intensified the antinociceptive effects of low-dose anandamide, 12.5 ng/paw, and PEA, 5 µg/paw. CONCLUSIONS: This study provides evidence that anandamide and PEA induce peripheral antinociception activating CB1 and CB2 cannabinoid receptors, respectively, stimulating an endogenous norepinephrine release that activates peripheral adrenoceptors inducing antinociception.


Asunto(s)
Analgésicos/farmacología , Agonistas de Receptores de Cannabinoides/farmacología , Norepinefrina/fisiología , Nervios Periféricos/efectos de los fármacos , Receptor Cannabinoide CB1/agonistas , Receptor Cannabinoide CB2/agonistas , Sistema Nervioso Simpático/efectos de los fármacos , Inhibidores de Captación Adrenérgica/farmacología , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Antagonistas Adrenérgicos beta/farmacología , Amidas , Animales , Ácidos Araquidónicos/antagonistas & inhibidores , Ácidos Araquidónicos/farmacología , Dinoprostona , Endocannabinoides/antagonistas & inhibidores , Endocannabinoides/farmacología , Etanolaminas/antagonistas & inhibidores , Etanolaminas/farmacología , Masculino , Morfolinas/farmacología , Dimensión del Dolor/efectos de los fármacos , Ácidos Palmíticos/antagonistas & inhibidores , Ácidos Palmíticos/farmacología , Alcamidas Poliinsaturadas/antagonistas & inhibidores , Alcamidas Poliinsaturadas/farmacología , Prazosina/farmacología , Propranolol/farmacología , Ratas , Ratas Wistar , Reboxetina , Yohimbina/farmacología
19.
Behav Brain Res ; 240: 160-70, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23195112

RESUMEN

The rat exposure test (RET) is a prey (mouse)-predator (rat) situation that activates brain defensive areas and elicits hormonal and defensive behavior in the mouse. Here, we investigated possible correlations between the spatiotemporal [time spent in protected (home chamber and tunnel) and unprotected (surface) compartments and frequency of entries into the three compartments] and ethological [e.g., duration of protected and unprotected stretched-attend postures (SAP), duration of contact with the rat's compartment] measures (Experiment 1). Secondly, we investigated the effects of systemic treatment with pro- or anti-aversive drugs on the behavior that emerged from the factor analysis (Experiment 2). The effects of chronic (21 days) imipramine and fluoxetine on defensive behavior were also investigated (Experiment 3). Exp. 1 revealed that the time in the protected compartment, protected SAP and rat contacts loaded on factor 1 (defensive behavior), while the total entries and unprotected SAP loaded on factor 2 (locomotor activity). Exp. 2 showed that alprazolam (but not diazepam) selectively changed the defensive factor. Caffeine produced a mild proaversive-like effect, whereas yohimbine only decreased locomotor activity (total entries). Fluoxetine (but not imipramine) produced a weak proaversive-like effect. 5-HT(1A)/5-HT(2) receptor ligands did not change any behavioral measure. In Exp. 3, chronic fluoxetine (but not imipramine) attenuated the defensive behavior factor without changing locomotion. Given that the defensive factor was sensitive to drugs known to attenuate (alprazolam and chronic fluoxetine) and induce (caffeine) panic attack, we suggest the RET as a useful test to assess the effects of panicolytic and panicogenic drugs.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Ansiolíticos/farmacología , Antidepresivos/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Reacción de Fuga/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Alprazolam/farmacología , Animales , Cafeína/farmacología , Diazepam/farmacología , Análisis Factorial , Fluoxetina/farmacología , Cadena Alimentaria , Imipramina/farmacología , Masculino , Ratones , Postura , Conducta Predatoria/fisiología , Ratas , Ratas Long-Evans , Factores de Tiempo , Yohimbina/farmacología
20.
J Alzheimers Dis ; 34(2): 509-18, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23241554

RESUMEN

Intracerebroventricular (icv) streptozotocin (STZ) administration induces pathological and behavioral alterations similar to those observed in Alzheimer's disease (AD) and is thus considered an experimental model of sporadic AD. Since caffeine (an adenosine receptor antagonist) and selective antagonists of adenosine A2A receptors modify the course of memory impairment in different amyloid-ß-based experimental models of AD, we now tested the impact of caffeine on STZ-induced dementia and associated neurodegeneration in the hippocampus as well as on the expression and density of adenosine receptors. Adult male rats received a bilateral infusion of saline or STZ (3 mg/kg, icv), which triggered memory deficits after four weeks, as gauged by impaired object recognition memory. This was accompanied by a reduced NeuN immunoreactivity in the hippocampal CA1 region and an increased expression and density of adenosine A2A receptors (A2AR), but not A1R, in the hippocampus. Caffeine consumption (1 g/L in the drinking water starting 2 weeks before the STZ challenge) prevented the STZ-induced memory impairment and neurodegeneration as well as the upregulation of A2AR. These findings provide the first demonstration that caffeine prevents sporadic dementia and implicate the control of central A2AR as its likely mechanism of action.


Asunto(s)
Cafeína/administración & dosificación , Demencia/prevención & control , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Trastornos de la Memoria/prevención & control , Receptor de Adenosina A2A , Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Animales , Demencia/metabolismo , Demencia/patología , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Trastornos de la Memoria/patología , Neuronas/efectos de los fármacos , Neuronas/patología , Ratas , Ratas Wistar , Receptor de Adenosina A2A/biosíntesis , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA