RESUMEN
OBJECTIVE: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. METHODS: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. RESULTS: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. CONCLUSION: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.
Asunto(s)
Amitriptilina/farmacología , Antidepresivos/farmacología , Fluoxetina/farmacología , Vena Safena/efectos de los fármacos , Vena Safena/trasplante , Tranilcipromina/farmacología , Clorhidrato de Venlafaxina/farmacología , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Puente de Arteria Coronaria/métodos , Endotelio Vascular/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/efectos de los fármacos , Valores de Referencia , Trasplantes/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Vena Safena/efectos de los fármacos , Vena Safena/trasplante , Tranilcipromina/farmacología , Fluoxetina/farmacología , Amitriptilina/farmacología , Antidepresivos/farmacología , Valores de Referencia , Vasodilatación/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Puente de Arteria Coronaria/métodos , Análisis de Varianza , Trasplantes/efectos de los fármacos , Clorhidrato de Venlafaxina/farmacología , Músculo Liso Vascular/efectos de los fármacosRESUMEN
The present work was addressed to study a possible relationship between monoamine oxidase (MAO) and the thyroid iodide transport mechanism. Normal rats treated with clorgyline (a selective MAO-A inhibitor) or tranylcypromine (a non-selective MAO inhibitor) showed a significantly diminished thyroid MAO activity, while deprenyl and pargyline (MAO-B inhibitors) did not modify the thyroidal enzyme activity with respect to the control group. Under these conditions, in vivo iodide transport was reduced both by clorgyline and tranylcypromine administration whereas it remained unchanged after treatment with MAO-B inhibitors. The effect of MAO inhibitors on thyroid MAO activity and in vivo iodide transport was also evaluated in rats treated with exogenous thyrotrophin (TSH) after endogenous TSH secretion blockade produced by T4 administration. In this condition, thyroid MAO activity was significantly lowered by clorgyline and was not modified by deprenyl. In contrast to the results observed in normal rats, in vivo iodide transport in TSH-treated rats remained unaltered after treatment either with clorgyline or deprenyl. MAO activity evaluated in bovine thyroid follicles in primary culture was highly sensitive to low concentrations of clorgyline (< 10 nmol/l) and relatively insensitive to deprenyl, a finding that indicates a predominance of the MAO-A isoform in the follicular cells in culture. When clorgyline (0.1 and 1 mumol/l) or deprenyl (1 mumol/l) were added to the culture medium, no modifications in the active transport of iodide were observed. These results indicate the absence of a direct linkage between thyroid MAO activity and the active iodide transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Yoduros/metabolismo , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo , Glándula Tiroides/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Clorgilina/farmacología , Masculino , Técnicas de Cultivo de Órganos , Pargilina/farmacología , Ratas , Ratas Wistar , Selegilina/farmacología , Glándula Tiroides/efectos de los fármacos , Tranilcipromina/farmacologíaRESUMEN
The effects of IVT serotonin [5-hydroxytryptamine (5-HT)] and dopamine (DA) administration have been studied in rats and marmosets (Callithrix jacchus). In rats, 5-HT (114 and 170 micrograms/10 microliters) produced the same behavioral effects observed after IP administration of its precursors and agonists. The same doses of 5-HT used for rats produced only part of the behavioral effects in marmosets after IP administration of 5-HT precursors and agonists. Ataxia, vomiting, and decreased motor activity were observed, but not drowsiness or teeth-chattering. However, IVT administration of DA (400 micrograms/10 microliters dose) produced head movements or checking, ataxia, tongue out, and decreased motor activity. These findings differ from those observed after IP administration of l-DOPA and DA agonists, which increase motor activity.
Asunto(s)
Conducta Animal/efectos de los fármacos , Dopamina/farmacología , Serotonina/farmacología , Animales , Callithrix , Dopamina/administración & dosificación , Femenino , Inyecciones Intraperitoneales , Inyecciones Intraventriculares , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Wistar , Receptores Dopaminérgicos/efectos de los fármacos , Receptores de Serotonina/efectos de los fármacos , Serotonina/administración & dosificación , Especificidad de la Especie , Tranilcipromina/farmacologíaRESUMEN
In view of existing reports documenting that "in vitro" norepinephrine (NE) contracts ring-shaped rat aortic preparations, whereas it relaxes arterial strips mounted in longitudinal fashion within an organ bath: it was decided to explore possible reasons which may account for such disparate actions of the same agonist on the same tissue. Isolated rings (circular preparations) obtained from rat thoracic aortae responded to increasing concentrations of NE with dose-dependent tonic enhancement, not significantly affected by the presence of indomethacin (10(-6)M); whereas, preincubation with phentolamine (10(-6)M), yohimbine (10(-7)M) or prazosin (10(-8)M), shifted significantly to the right points of the positive inotropic dose-response curve for NE. On the contrary longitudinally mounted preparations of rat aortic stips, reacted to increasing concentrations of NE with dose-dependent relaxation, an effect not modified by the presence of a beta-adrenoreceptor blocker, namely propranolol (10(-6)M). However, in presence of alpha-adrenoreceptor blockers, such as phentolamine (10(-6)M), yohimbine (10(-7)M) or prazosin (10(-8)M), the negative inotropic dose-response curve for NE was shifted to the right whereas in the presence of indomethacin (10(-6)M) or of tranylcypromine (2.5 x 10(-4)M), the NE-induced relaxation was either abolished or significantly displaced to the right, respectively. In another series of experiments the generation of labelled 6-keto-prostaglandin F1 alpha (the most important non-enzymatic metabolite of prostacyclin) by chopped rat aortae incubated for one hour with (1-14C)-arachidonic acid, was explored and found to be significantly enhanced by the delivery of NE (3 x 10(-6)M). The present evidence suggests that NE acting on alpha-adrenoreceptors, induces in longitudinal and in chopped arterial preparations, but not in aortic rings, an inhibitory relaxing factor, presumably produced by the endothelium. This factor is probably prostacyclin for the relaxing effects of the agonist were negatively influenced by indomethacin and by tranylcypromine, two known antagonists of PGI2 formation. In vascular rings (circular arterial preparations) the tonic stimulatory action of NE (not affected by preincubation with indomethacin) was the only evident inotropic effect of the agonist presumably because the extensive handling of the tissue as well as the anchoring procedure followed to mount arterial preparations within the bath for contractile recordings, may produce de-endothelization.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Epoprostenol/fisiología , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Norepinefrina/farmacología , 6-Cetoprostaglandina F1 alfa/biosíntesis , Animales , Aorta Torácica/fisiología , Ácido Araquidónico , Ácidos Araquidónicos/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Indometacina/farmacología , Relajación Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Fentolamina/farmacología , Prazosina/farmacología , Propranolol/farmacología , Ratas , Ratas Endogámicas , Tranilcipromina/farmacología , Yohimbina/farmacologíaRESUMEN
The isolated right rat atrium was used to investigate the chronotropic effects of dl-tranylcypromine and its d- and l-isomers. The concentration-effect curves of the three compounds were similar. The response of the preparation to the three drugs was completely blocked by pretreatment of the animal with reserpine, thus indicating an indirect effect of the drugs by the release of the natural mediator. Cocaine present in the bathing fluid partially antagonized the effect of dl-tranylcypromine and its isomers. It is concluded that the accumulation of the different forms of the drug by neural structures and the subsequent release of the neurotransmitter are not stereospecific processes. Furthermore it is suggested that the efflux of the neurotransmitter in the rat atrium may be carrier-mediated, and that this process is inhibited by cocaine.
Asunto(s)
Atrios Cardíacos/efectos de los fármacos , Tranilcipromina/metabolismo , Animales , Cocaína/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas , Reserpina/farmacología , Estereoisomerismo , Tranilcipromina/antagonistas & inhibidores , Tranilcipromina/farmacologíaRESUMEN
The anticholinesterase (antiChE) activity of ranylcypromine (TRCY) and its isomers was studied by employing dog plasma as a cholinesterase source. Changes in arterial blood pressure, elicited by a mixture of acetylcholine (Ach) and dog plasma with or without those drugs, as an indicator of their anti ChE activity were monitored. When TRCY or one of its isomers was present in concentrations higher than 125 microM in plasma containing Ach, the hypotensive effect of the latter was preserved. Such findings provide experimental evidence that TRCY and its isomers may exert antiChE activity.
Asunto(s)
Inhibidores de la Colinesterasa , Tranilcipromina/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Perros , Femenino , Isomerismo , Masculino , Tranilcipromina/administración & dosificaciónRESUMEN
The effects of bis (4-methyl-l-homopiperazinyltio - carbonyl) disulphide (FLA-63), haloperidol, reserpine and tranylcypromine on physostigmine-inducedhyperactivity in rats were studied using jiggle platforms to measure motor activity levels. Haloperidol (0.025 mg/kg). On the other hand FLA-63 (2.5 mg/kg) and tranylcypromine (20 mg/kg) attenuated the effect of physostigmine during the first thirty minutes of testing and caused a potentiation during the next thirty minutes. All drugs were administered intraperitoneally. These results support the hypothesis of an interaction between the cholinergic and catecholminergic systems in the central nervous system (AU)