A novel nasal co-loaded loratadine and sulpiride nanoemulsion with improved downregulation of TNF-α, TGF-ß and IL-1 in rabbit models of ovalbumin-induced allergic rhinitis.

PURPOSE: The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management. METHODS: Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-α, TGF-ß and IL-1. RESULTS: Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2 ± 0.2 nm), low PDI (0.35 ± 0.0) and appropriate Zeta Potential (-23.3 ± 0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-α, IL-1 and TGF-ß significantly decreased from 9.59 ± 1.06, 4.15 ± 0.02 and 4.15 ± 0.02 to 1.28 ± 0.02, 1.93 ± 0.06 and 1.56 ± 0.02 respectively after treatment with the selected nanoemulsion formulation. CONCLUSION: The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.

Probiotics Affect One-Carbon Metabolites and Catecholamines in a Genetic Rat Model of Depression.

SCOPE: Probiotics may influence one-carbon (C1) metabolism, neurotransmitters, liver function markers, or behavior. METHODS AND RESULTS: Male adult Flinders Sensitive Line rats (model of depression, FSL; n = 22) received Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (109 or 1010 colony-forming units per day) or vehicle for 10 weeks. The controls, Flinders Resistant Line rats (FRL, n = 8), only received vehicle. C1-related metabolites were measured in plasma, urine, and different tissues. Monoamine concentrations were measured in plasma, hippocampus, and prefrontal cortex. Vehicle-treated FSL rats had higher plasma concentrations of betaine, choline, and dimethylglycine, but lower plasma homocysteine and liver S-adenosylmethionine (SAM) than FRLs. FSL rats receiving high-dose probiotics had lower plasma betaine and higher liver SAM compared to vehicle-treated FSL rats. FSLs had higher concentrations of norepinephrine, dopamine, and serotonin than FRLs across various brain regions. Probiotics decreased plasma dopamine in FSLs in a dose-dependent manner. There were no detectable changes in liver function markers or behavior. CONCLUSIONS: Probiotics reduced the flow of methyl groups via betaine, increased liver SAM, and decreased plasma dopamine and norepinephrine. Since these changes in methylation and catecholamine pathways are known to be involved in several diseases, future investigation of the effect of probiotics is warranted.

Monoaminergic neurotransmission is mediating the antidepressant-like effects of Passiflora edulis Sims fo. edulis.

The genus Passiflora is popularly used to treat anxiety. Recent studies showed antidepressant-like effects of two varieties of P. edulis (edulis and flavicarpa) in mice. However, the mechanisms of antidepressant actions are still unknown. Here, the effects of P. edulis fo. edulis aqueous extract (AE, 100-300mg/kg, po), and ethyl acetate (AcOEt, 25-50mg/kg, po), butanol (BuOH, 25-50mg/kg, po) and residual aqueous (25-100mg/kg, po) fractions were investigated in the mouse forced swimming test. In addition, the involvement of monoamines in the P. edulis fractions-induced antidepressant actions was approached. HPLC analyses showed that AcOEt and BuOH, but not residual, fractions shared with AE the main peaks between 25 and 70min (UV 340nm), which are suggestive of flavonoids. Nortriptyline and fluoxetine reduced the immobility time and similar results were observed for AE, AcOEt and BuOH but not residual fractions. PCPA (inhibitor of 5-HT synthesis), AMPT (inhibitor of catecholamine synthesis) and sulpiride (selective D2 receptor antagonist), but not DSP-4 (noradrenergic neurotoxin), blocked the antidepressant actions of AcOEt and BuOH. In conclusion, AcOEt and BuOH fractions shared with AE similar phytochemical composition and antidepressant actions. Preserved 5-HT and dopamine transmissions were required for the antidepressant effects of P. edulis fractions.

Acupuncture Attenuated Vascular Dementia-Induced Hippocampal Long-Term Potentiation Impairments via Activation of D1/D5 Receptors.

BACKGROUND AND PURPOSE: Emerging evidence suggests that acupuncture could improve cognitive impairment in vascular dementia by enhancing synaptic plasticity in the hippocampus. The purpose of this study is to investigate whether dopamine, a key mediator of synaptic plasticity, is involved in this cognitive improvement. METHODS: Vascular dementia model was established by bilateral common carotid arteries occlusion in male Wistar rats. Three days after the operation, animals received acupuncture treatment for 2 weeks, once daily. The D1/D5 receptors antagonist SCH23390 was administered intraperitoneally 15 minutes before each acupuncture treatment. Morris water maze was examined after acupuncture. Long-term potentiation was studied by an electrophysiological technique. Dopamine and metabolites levels were detected by microdialysis and high-performance liquid chromatography from brain tissue. The expression of D1R and D5R was analyzed by immunofluorescence. RESULTS: Acupuncture remarkably reversed cognitive deficits in 2-vessel occlusion model (2VO) rats, and the acupuncture points Zusanli (ST36) and Baihui (GV20) were confirmed to be the most effective combination. Electrophysiological recording data showed that 2VO-induced impairments of long-term potentiation were prevented by acupuncture. In addition, acupuncture promoted the release of dopamine and its major metabolites in the hippocampus of 2VO rats. The immunofluorescence experiment showed that the decrease of D1R and D5R in hippocampal dentate gyrus region of 2VO rats was reversed by acupuncture. Furthermore, we found that the effects of acupuncture against 2VO-induced impairments in cognition and synaptic plasticity were abolished by SCH23390. CONCLUSIONS: Improvement in cognition and hippocampal synaptic plasticity induced by acupuncture was achieved via activation of D1/D5 receptors in 2VO rats.

Combination of thioridazine and dicloxacillin as a possible treatment strategy of staphylococci.

We have previously shown that the phenothiazine, thioridazine, acts in synergy with the beta-lactam antibiotic, dicloxacillin, to kill methicillin-resistant Staphylococcus aureus. In this study, we investigated whether synergy by combining these two drugs could also be observed in vancomycin intermediate susceptible S. aureus (VISA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Synergy was observed in three of four tested VISA strains, suggesting that the thickening of cell wall does not interfere with the effects of thioridazine. In S. epidermidis, no synergy was observed in all tested strains, suggesting that synergy by combining thioridazine and dicloxacillin is isolated to S. aureus species.

Identification and management of tardive dyskinesia: A case series and literature review.

Tardive dyskinesia (TD) is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking dopamine receptor-blocking agents. The pathophysiology of TD is complex, multifactorial and still not fully understood. Although there is no identified effective and standard treatment for TD, several agents have been tried for the management of this motor disturbance. The aim of this case series is to review the literature in regard to the identification, diagnosis and the treatment of TD with anticholinergics, anticholinergic medication withdrawal, cholinergic agents, botulinum toxin intramuscular injections, tetrabenazine, levetiracetam, propranolol and zolpidem, and to describe one case of TD that responded favorably to clonazepam and two cases of TD that responded favorably to Ginkgo biloba.

Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain.

Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.

Effect of peripheral D2 dopamine receptor antagonist domperidone on metabolism, feeding behavior, and locomotor activity of rats.

We studied the possibility of activation of the central dopaminergic system compartment by modulating activity of D2 dopamine receptors in the gastrointestinal tract with domperidone, an antagonist not crossing the blood-brain barrier. Intragastric administration of 0.1 mg/kg domperidone to rats was followed by a significant decrease in feeding behavior and stimulation of basal metabolism, but had no effect on locomotor activity of animals in a Phenomaster system. These effects are typical of psychostimulant agents that stimulate dopamine release from nerve endings in the nucleus accumbens and some regions of the brain cortex. Our results indicate that physiological functions associated with activity of the central dopaminergic system can be modulated through peripheral dopamine receptors.

Effects of SKF-83566 and haloperidol on performance on progressive ratio schedules maintained by sucrose and corn oil reinforcement: quantitative analysis using a new model derived from the Mathematical Principles of Reinforcement (MPR).

RATIONALE: Mathematical models can assist the interpretation of the effects of interventions on schedule-controlled behaviour and help to differentiate between processes that may be confounded in traditional performance measures such as response rate and the breakpoint in progressive ratio (PR) schedules. OBJECTIVE: The effects of a D1-like dopamine receptor antagonist, 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide (SKF-83566), and a D2-like receptor antagonist, haloperidol, on rats' performance on PR schedules maintained by sucrose and corn oil reinforcers were assessed using a new model derived from Killeen's (Behav Brain Sci 17:105-172, 1994) Mathematical Principles of Reinforcement. METHOD: Separate groups of rats were trained under a PR schedule using sucrose or corn oil reinforcers. SKF-83566 (0.015 and 0.03 mg kg(-1)) and haloperidol (0.05 and 0.1 mg kg(-1)) were administered intraperitoneally (five administrations of each treatment). Running and overall response rates in successive ratios were analysed using the new model, and estimates of the model's parameters were compared between treatments. RESULTS: Haloperidol reduced a (the parameter expressing incentive value) in the case of both reinforcers, but did not affect the parameters related to response time and post-reinforcement pausing. SKF-83566 reduced a and k (the parameter expressing sensitivity of post-reinforcement pausing to the prior inter-reinforcement interval) in the case of sucrose, but did not affect any of the parameters in the case of corn oil. CONCLUSIONS: The results are consistent with the hypothesis that blockade of both D1-like and D2-like receptors reduces the incentive value of sucrose, whereas the incentive value of corn oil is more sensitive to blockade of D2-like than D1-like receptors.

Dopamine D2 receptor antagonism suppresses tau aggregation and neurotoxicity.

BACKGROUND: Tauopathies, including Alzheimer's disease and frontotemporal dementia, are diseases characterized by the formation of pathological tau protein aggregates in the brain and progressive neurodegeneration. Presently no effective disease-modifying treatments exist for tauopathies. METHODS: To identify drugs targeting tau neurotoxicity, we have used a Caenorhabditis elegans model of tauopathy to screen a drug library containing 1120 compounds approved for human use for the ability to suppress tau-induced behavioral effects. RESULTS: One compound, the typical antipsychotic azaperone, improved the motility of tau transgenic worms, reduced levels of insoluble tau, and was protective against neurodegeneration. We found that azaperone reduces insoluble tau in a human cell culture model of tau aggregation and that other antipsychotic drugs (flupenthixol, perphenazine, and zotepine) also ameliorate the effects of tau expression in both models. CONCLUSIONS: Reduction of dopamine signaling through the dopamine D2 receptor with the use of gene knockouts in Caenorhabditis elegans or RNA interference knockdown in human cell culture has similar protective effects against tau toxicity. These results suggest dopamine D2 receptor antagonism holds promise as a potential neuroprotective strategy for targeting tau aggregation and neurotoxicity.

Effects of microinjections of apomorphine and haloperidol into the inferior colliculus on prepulse inhibition of the acoustic startle reflex in rat.

Prepulse inhibition (PPI) is the reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus and is an operational measure of sensorimotor gating. PPI is impaired in schizophrenia patients and in rats with central dopamine (DA) activation. The inferior colliculus (IC) is a critical part of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. The aim of this study was to elucidate the role of DA transmission of the IC on the development of acoustic PPI. Bilateral microinjections of apomorphine (9.0 µg/0.5 µL), an agonist of D(2) receptors, into the IC disrupted PPI while microinjections of haloperidol (0.5 µg/0.5 µL), an antagonist of D(2) receptors, into this structure did not alter PPI. These results suggest that dopamine-mediated mechanisms of the IC are involved in the expression of PPI in rodents.

Wild ginseng attenuates repeated morphine-induced behavioral sensitization in rats.

Many studies have suggested that the behavioral and reinforcing effects of morphine are induced by hyperactivation of the mesolimbic dopaminergic system, which results in increases in locomotor activity, c-Fos expression in the nucleus accumbens (NAc), and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). In order to investigate the effect of wild ginseng (WG) on treating morphine addiction, we examined the behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. Intraperitioneal injection of WG (100 and 200 mg/kg), 30 min before administration of a daily injection of morphine (40 mg/kg, s.c.), significantly inhibited morphine-induced increases in c-Fos expression in NAc and TH expression in VTA as well as in locomotor activity, as compared with Panax ginseng. It was demonstrated that the inhibitory effect of WG on the behavioral sensitization after repeated exposure to morphine was closely associated with the reduction of dopamine biosynthesis and postsynaptic neuronal activity. It suggests that WG extract may be effective for inhibiting the behavioral effects of morphine by possibly modulating the central dopaminergic system and that WG might be a useful resource to develop an agent for preventing and treating morphine addiction.

Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats.

Cocaine addiction is characterized by a persistently heightened susceptibility to drug relapse. For this reason, the identification of medications that prevent drug relapse is a critical goal of drug abuse research. Drug re-exposure, the onset of stressful life events, and exposure to cues previously associated with drug use have been identified as determinants of relapse in humans and have been found to reinstate extinguished cocaine seeking in rats. This study examined the effects of acute oral (gavage) administration of levo-tetrahydropalmatine (l-THP), a tetrahydroprotoberberine isoquinoline with a pharmacological profile that includes antagonism of D1, D2 and D3 dopamine receptors, on the reinstatement of extinguished cocaine seeking by a cocaine challenge (10mg/kg, ip), a stressor (uncontrollable electric footshock [EFS]) or response-contingent exposure to a stimulus (tone and light complex) previously associated with drug delivery in male Sprague-Dawley rats. Extinguished drug seeking was reinstated by ip cocaine, EFS, or response-contingent presentation of drug-associated cues in vehicle-pretreated rats following extinction of iv cocaine self-adminisration. Oral administration of either 3.0 or 10.0mg/kg l-THP 1h prior to reinstatement testing significantly attenuated reinstatement by each of the stimuli. Food-reinforced responding and baseline post-extinction responding were significantly attenuated at the 10.0, but not the 3.0mg/kg, l-THP dose, indicating that the effects of 3mg/kg l-THP on reinstatement were likely independent of non-specific motor impairment. These findings further suggest that l-THP may have utility for the treatment of cocaine addiction.

Bee venom reduces neuroinflammation in the MPTP-induced model of Parkinson's disease.

AIM: This study was designed to investigate the anti-inflammatory effects of bee venom (BV) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD). METHOD: MPTP was administered by intraperitoneal (IP) injection at 2-hr intervals over an 8-hr period. Mice were then subjected to BV subcutaneous injection and sacrificed on days 1 and 3 following the final MPTP injection. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) was assessed by tyrosine hydroxylase (TH) immunohistochemistry. Microglial activation was measured by immunohistochemistry for macrophage antigen complex-1 (MAC-1) and inducible nitric oxide synthase (iNOS). The staining intensities of MAC-1 and iNOS were quantified with respect to optical density. RESULT: In animals treated with MPTP, the survival percentages of TH+ cells in the SNpc were 32% on day 1 and 46% on day 3 compared with normal mice. In BV-treated mice, the survival percentages of TH+ cells improved to 70% on day 1 and 78% on day 3 compared with normal mice. BV treatment also resulted in reduced expression of the inflammation markers MAC-1 and iNOS in the SNpc. CONCLUSION: These data suggest that BV injection may have a neuroprotective effect that attenuates the activation of the microglial response, which has implications for the treatment of PD.

Partial agonists in schizophrenia--why some work and others do not: insights from preclinical animal models.

While dopamine D2 receptor partial agonists (PAs) have been long considered for treating schizophrenia, only one, aripiprazole, is clinically available for therapeutic use. This raises critically important questions as to what is unique about aripiprazole and to what extent animal models can predict therapeutic success. A number of PAs whose clinical fate is known: aripiprazole, preclamol, terguride, OPC-4392 and bifeprunox were compared to haloperidol (a reference antipsychotic) in several convergent preclinical animal models; i.e. amphetamine-induced locomotion (AIL) and conditioned avoidance response (CAR), predictive of antipsychotic effects; unilateral nigrostriatal lesioned rats, a model of hypo-dopaminergia; striatal Fos induction, a molecular marker for antipsychotic activity; and side-effects common to this class of drugs: catalepsy (motor side-effects) and prolactaemia. The results were compared across drugs with reference to their measured striatal D2 receptor occupancy. All the PAs occupied striatal D2 receptors in a dose dependent manner, inhibited AIL and CAR, and lacked motor side-effects or prolactinaemia despite D2 receptor occupancy exceeding 80%. At comparative doses, aripiprazole distinguished itself from the other PAs by causing the least rotation in the hypo-dopaminergic model (indicating the least intrinsic activity) and showed the highest Fos expression in the nucleus accumbens (indicating functional D2 antagonism). Although a number of PAs are active in antipsychotic animal models, not all of them succeed. Given that only aripiprazole is clinically available, it can be inferred that low functional intrinsic activity coupled with sufficient functional antagonism as reflected in the animal models may be a marker of success.

D(1)/D(2) receptor-targeting L-stepholidine, an active ingredient of the Chinese herb Stephonia, induces non-rapid eye movement sleep in mice.

L-stepholidine, an active ingredient of the Chinese herb Stephonia, is the first compound known to have mixed dopamine D(1) receptor agonist/D(2) antagonist properties and to be a potential treatment medication for schizophrenia. In schizophrenic patients insomnia is a common symptom and could be partly related to the presumed over-activity of the dopaminergic system. To elucidate whether stepholidine modulates sleep behaviors, we observed its effects on sleep-wake profiles in mice. The results showed that stepholidine administered i.p. at doses of 20, 40 or 80 mg/kg significantly shortened the sleep latency to non-rapid eye movement (non-REM, NREM) sleep, increased the amount of NREM sleep, and prolonged the duration of NREM sleep episodes, with a concomitant reduction in the amount of wakefulness. Stepholidine at doses of 40 and 80 mg/kg increased the number of state transitions from wakefulness to NREM sleep and subsequently from NREM sleep to wakefulness. However, stepholidine had no effect on either the amount of REM sleep or electroencephalogram power density of either NREM or REM sleep. Immunohistochemistry study showed that stepholidine dose-dependently increased c-Fos expression in neurons of the ventrolateral preoptic area, a sleep center in the anterior hypothalamus, as compared with the vehicle control. These results indicate that stepholidine initiates and maintains NREM sleep with activation of the sleep center in mice, suggesting its potential application for the treatment of insomnia.

Medical therapy of adrenocortical tumors.

Medical therapy is but one of a multiarm, multispecialty approach that is needed in order to successfully treat adrenocortical tumors. The role of surgery, radiation therapy, radiofrequency ablation, and the need for a team approach for the care of the patient cannot be over-emphasized. In this article current and potential future medical therapies for adrenocortical tumors are reviewed.

Dopaminergic activation excites rat lateral habenular neurons in vivo.

The lateral habenular complex (LHb) of the epithalamus is part of a dorsal diencephalic conduction system connecting basal forebrain with regulatory midbrain nuclei. The LHb has been implicated in the regulation of ascending monoaminergic transmission, particularly midbrain dopaminergic neuronal activity. Here, we have investigated whether the LHb in turn is subject to dopaminergic modulation. Alterations in spontaneous neuronal activity within the LHb following systemic application of dopaminergic drugs have been examined in anesthetized rats using extracellular single unit recordings. The administration of apomorphine (2 mg/kg) resulted in an excitation of individual LHb neurons. On average, the spontaneous action potential firing of the LHb neurons was increased by 39%. However, the apomorphine effect showed marked topographic differences within the LHb. Particularly, a small subset of neurons in the lateral division of the LHb, which was localized within the oval subnucleus, showed an apomorphine-mediated increase in discharge frequency by 96%. In contrast, spontaneous discharge of neurons within other areas of the lateral division was not modified. Likewise, within the medial division of the LHb, a region that preferentially receives projections from dopaminergic midbrain nuclei, the majority of neurons failed to show apomorphine-mediated alterations in action potential firing. However, within the superior subnucleus of this division, an area with yet unclear afferent supply, spontaneous neuronal firing was enhanced by 56%. The apomorphine-mediated excitation of LHb neurons was antagonized by coapplication of haloperidol (2 mg/kg), which alone did not alter spontaneous action potential firing of individual LHb neurons. The present study demonstrates that spontaneous activity of distinct subsets of neurons within the LHb is strongly enhanced by systemic activation of dopaminergic receptors. Despite the small sample size, the data suggest that this dopaminergic modulation shows a topographic specificity. Therefore, the results support the hypothesis of a functional subnuclear organization of the rat habenular complex.

Dopaminergic modulation of reproductive behavior and activity in male zebra finches.

We previously demonstrated that hormone treatments which stimulate female-directed singing increased levels and turnover of dopamine (DA) in brain areas controlling the motor patterning of song. To help determine how DA affects singing, we quantified the effects of treating adult male finches with the D1/D2 receptor antagonist cis-flupenthixol. Adult males were given subcutaneous silastic implants of androgen, in case drug treatment interfered with androgen secretion. One week later, they were tested with females. Males were divided into three groups matched for levels of courtship singing. Males were then subcutaneously implanted with osmotic minipumps containing either saline, a low, or a high dose of cis-flupenthixol. Each male was tested with a different female 5 and 10 days after implantation to determine how this D1/D2 receptor antagonist affected behavior. Both drug doses affected female-directed singing 5 days after initiation of treatment. High-dose males sang to females significantly less often than males in the other two groups. Low-dose males showed fewer high-intensity courtship displays in which males dance towards females as they sing. These effects on courtship singing were not seen at day 10, though other behavioral effects were seen at this time. Male beak wipes, rocks, following females and female withdrawals from males were also affected by drug treatment. General activity in the home cage was decreased by day 11. These data demonstrate that singing and several other female-directed behaviors are sensitive to perturbations in DA receptor function.

Continuous infusion in adult females dogs submitted to ovariohysterectomy with midazolam-xylazine and/or medetomidine pre-treated with methotrimeprazine and buprenorphine

PURPOSE: To compare, by continuous infusion of ketamine or medetomidine combined to methotrimeprazine and buprenorphine, ketamine and midazolam, the degree of hypnosis, myorelaxation, anesthetic quality and surgical feasibility through evaluation of possible parametric alterations and recovery quality. METHODS: 20 healthy adult females dogs, aged 3 to 5 years, body weight between 7 and 15 kg, were assigned randomly and homogenously to 2 groups of 10 animals each (n=10), group 1 (G1) and group 2 (G2), respectively. Animals of G1 were subjected to a pre-treatment with intravenous 1.0 mg/kg methotrimeprazine and or 3ì/kg. After 15 minutes, a 5.0 mg/kg ketamine and 0.2 mg/kg midazolam were intravenously injected. Immediately after induction, an anesthetic combination of 0.4 mg/kg/h midazolam, 20 mg/kg/h ketamine and 1.0 mg/kg/h xylazine, was continuously and intravenously administered for 30 minutes. The same techniques were used in G2 except for the substitution of xylazine for 30ìg/kg/h medetomidine. RESULTS: In G1 there was a 1st and 2nd degree atrioventricular heart block, a longer recovery period and lower quality. In G2 a 1st degree atrioventricular heart block occurred but isolated and ephemeral. CONCLUSIONS: The continuous infusion method, besides reducing drugs utilization, prevented collateral effects allowing a more tranquil recovery with no excitations, both protocols permitted the surgical procedure (ovary-hysterectomy) bringing about a reduction in hypnosis and an accentuated myorelaxation. Xylazine and medetomidine showed a similar pharmacodynamic behavior but with different clinical aspects. The electrocardiographic alterations observed in G2 and in a lower degree in G1 must be well studied. Describers: dogs, ketamine, methotrimeprazine, medetomidine, midazolam and xylazine.

OBJETIVO: Comparar através de infusão contínua de xilazina ou medetomidina associada à metotrimeprazina e buprenorfina, cetamina e midazolam, o grau de hipnose, miorrelaxamento e qualidade anestésica e a viabilidade cirúrgica, avaliando eventuais alterações paramétricas e qualidade de recuperação. MÉTODOS: Foram utilizados 20 cães fêmeas, adultas, hígidas (3 a 5 anos de idade) com peso corporal entre 7 e 15 quilos, escolhidas e distribuídas aleatoriamente de forma homogênea em 2 grupos de 10 animais cada, (n=10) sendo estes designados por Grupo 1 (G1), e Grupo 2 (G 2). Em G1, os animais foram submetidos a um pré-tratamento com metotrimeprazina na dose de 1,0 mg/kg e buprenorfina na dose de 0,003mg/kg ou 3 µg/kg intravenoso. Decorridos 15 minutos, administrou-se cetamina na dose de 5,0 mg/kg e midazolam na dose de 0,2 mg/kg intravenoso. Imediatamente após a indução iniciou-se administração contínua, por um período de 30 minutos, da associação anestésica de midazolam 0,4 mg/kg/h, cetamina 20mg/kg/h e xilazina 1,0 mg/kg/h IV. Em G 2 utilizou-se a mesma técnica empregada em G1 substituindo-se, a xilazina pela medetomidina na dose de 30µg/kg/h. RESULTADOS: Verificou-se em G1 bloqueio átrio-ventricular de primeiro e segundo grau, período de recuperação mais longo além de menor qualidade. Em G 2 observou-se bloqueio átrio-ventricular de primeiro grau isolado e de ação fugaz. CONCLUSÕES: Ao se aplicar o método de infusão contínua, além da redução dos fármacos aplicados, evitaram-se efeitos colaterais permitindo uma recuperação mais tranqüila e isenta de excitações, ambos os protocolos permitiram a realização do ato cirúrgico (ovário-salpingo-histerectomia), causando uma redução da hipnose e um miorrelaxamento acentuado. A xilazina e a medetomidina apresentam um comportamento farmacodinâmico semelhante, porém com aspectos clínicos diferentes, as alterações eletrocardiográficas observadas em G 2 e em menor grau em G1 devem ser melhor estudadas.