Modulatory effects of taurine on jejunal contractility

Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

Efeitos hemodinâmicos do atracúrio e do cisatracúrio e o uso de difenidramina e cimetidina / Hemodynamic effects of atracurium and cisatracurium and the use of diphenhydramine and cimetidine / Efectos hemodinámicos del atracurio y del cisatracurio y el uso de la difenidramina y la cimetidina

Justificativa e objetivos: Haja visto que atracúrio pode causar hipotensão arterial no homem, investigaram-se os efeitos hemodinâmicos promovidos pelo atracúrio e pelo cisatracúrio e a proteção hemodinâmica conferida pela difenidramina e cimetidina em ratos. Método: 1) Ratos Wistar anestesiados com pentobarbital sódico e preparados de acordo com Brown e col. para avaliar doses de atracúrio e cisatracúrio para redução de T4/T1 da sequência de quatro estímulos maior ou igual a 95 por cento. 2) Avaliação das alterações hemodinâmicas de atracúrio e cisatracúrio por injeção venosa, medindo-se a pressão arterial sistêmica da artéria carótida e eletrocardiograma de ratos. 3) Observação de proteção hemodinâmica pelo tratamento prévio com difenidramina (2 mg.kg-1) e/ou cimetidina (4 mg.kg-1) por injeção venosa. Análise estatística: teste t de Student, ANOVA. Resultados: O atracúrio e o cisatracúrio não modificaram a pressão arterial média (PAM) nas doses de 1 mg.kg-1 e 0,25 mg.kg-1, respectivamente. Doses de 4 mg.kg-1 promoveram diminuição da PAM de 62,8 ± 4,5 por cento do controle para o atracúrio, e de 82,5 ± 2,3 por cento do controle para o cisatracúrio. Com difenidramina e cimetidina, a pressão sistólica diminuiu 95,4 ± 2,5 por cento do controle. Com cimetidina, pressão diastólica diminuiu 82,7 ± 8,4 por cento do controle. O efeito conjunto sobre as pressões sistólica e diastólica refletiu-se nos valores observados da PAM. Conclusões: A difenidramina e a cimetidina, isoladamente, não impediram a diminuição da pressão arterial média induzida pelo atracúrio. No entanto, associação destes dois fármacos foi eficaz na prevenção dos efeitos hemodinâmicos induzidos pelo atracúrio. O cisatracúrio nas doses do experimento não promoveu diminuição da pressão arterial que justificasse as medidas preventivas aplicadas nos grupos onde se utilizou o atracúrio.

Background and objectives: Since atracurium can cause hypotension in humans, the hemodynamic effects of atracurium and cisatracurium as well as the hemodynamic protection of diphenhydramine and cimetidine were investigated in rats. Methods: 1) Wistar rats were anesthetized with sodium pentobarbital and prepared according to Brown et al. to evaluate different doses of atracurium and cisatracurium in the reduction of T4/T1 equal or greater than 95 percent. 2) Assessment of the hemodynamic changes caused by the intravenous administration of atracurium and cisatracurium by monitoring the blood pressure in the carotid artery and the electrocardiogram of rats. 3) Observation of the hemodynamic protection of prior treatment with the intravenous administration of diphenhydramine (2 mg.kg-1) and/or cimetidine (4 mg.kg-1). Statistical analysis: Student t test and ANOVA. Results: Doses of 1 mg.kg-1 and 0.25 mg.kg-1 of atracurium and cisatracurium respectively did not change the mean arterial pressure (MAP). Doses of 4 mg.kg-1 of atracurium and cisatracurium decreased MAP to 62.8 ± 4.5 percent and 82.5 ± 2.3 percent respectively when compared to control levels. When the rats were pre-treated with diphenhydramine and cimetidine, diastolic pressure was reduced to 95.4 percent ± 2.5 percent. With cimetidine, diastolic pressure was reduced to 82.7 ± 8.4 percent when compared to the control group. The effects on systolic and diastolic blood pressure were reflected in the levels of MAP. Conclusions: The isolated administration of diphenhydramine and cimetidine did not prevent the reduction in mean arterial pressure induced by atracurium. However, the association of both drugs was able to prevent the hemodynamic effects of atracurium. The doses of cisatracurium used in this study did not cause a reduction in blood pressure significant enough to justify the use of the preventive measures used in the atracurium groups.

Justificativa y objetivos: Habida cuenta de que el atracurio puede causar hipotensión arterial en el hombre, se investigaron los efectos hemodinámicos promovidos por el atracurio y por el cisatracurio, y la protección hemodinámica dada por la difenidramina y la cimetidina en ratones. Método: 1) Ratones Wistar anestesiados con pentobarbital sódico y preparados de acuerdo con Brown y col. para evaluar las dosis de atracurio y cisatracurio para la reducción de T4/T1 de la secuencia de cuatro estímulos mayor o igual al 95 por ciento. 2) Evaluación de las alteraciones hemodinámicas del atracurio y el cisatracurio por inyección venosa, midiendo la presión arterial sistémica de la arteria carótida y electrocardiograma de ratones. 3) Observación de la protección hemodinámica por el tratamiento previo con difenidramina (2 mg.kg-1) y/o cimetidina (4 mg.kg-1) por inyección venosa. Análisis estadístico: test t de Student, ANOVA. Resultados: El atracurio y el cisatracurio no modificaron la presión arterial promedio (PAP) en las dosis de 1 mg.kg-1 y 0,25 mg.kg-1, respectivamente. Las dosis de 4 mg.kg-1 disminuyeron la PAP de 62,8 ± 4,5 por ciento del control para el atracurio, y de 82,5 ± 2,3 por ciento del control para el cisatracurio. Con la difenidramina y la cimetidina, la presión sistólica se redujo a 95,4 ± 2,5 por ciento del control. Con la cimetidina, la presión diastólica disminuyó 82,7 ± 8,4 por ciento del control. El efecto con-junto sobre las presiones sistólica y diastólica se reflejó en los valores observados de la PAP. Conclusiones: La difenidramina y la cimetidina, aisladamente, no impidieron la disminución de la presión arterial promedio inducida por el atracurio. Sin embargo, la asociación de esos de los fármacos fue eficaz en la prevención de los efectos hemodinámicos inducidos por el atracurio. El cisatracurio, en las dosis del experimento, no promovió una disminución de la presión arterial que justificase las medidas preventivas...

Influence of histamine and H1-receptor antagonists on ejaculated human spermatozoa: role of intrasperm Ca2+.

Histamine reduced sperm viability in a dose- and time-dependent manner, accompanied by rise in intrasperm Ca2+. Further, 2',4'-dichlorobenzamil hydrochloride (DBZ), a Na+-Ca2+ exchange inhibitor, known to elevate intrasperm Ca2+, potentiated both, elevation of intrasperm Ca2+ and spermicidal action of histamine. Pretreatment of sperm with very low doses of H1-receptor antagonists (chlorpheniramine, promethazine or diphenhydramine) prevented the histamine-induced elevation of intrasperm Ca2+ as well as its spermicidal action. However, pretreatment with famotidine, a H2-receptor antagonist did not produce such a protective action. The results strongly suggest that histamine elicits its spermicidal action via H1-receptors present on sperm cells.

Estudo da açäo depressora inespecífica do suco extraído das folhas de Bryophyllum calcynum Salisb. (Crassulaceae) sobre o sistema nervoso central: comparaçäo com os efeitos da difenidramina / Study on the innespecific depressive action of the leaves juice of Bryophillum calycinum Salisb. (Crassulaceae) in the central nervous system: comparison whith diphenhydramine effects

Bryophyllum calcynum Salisb (Crassulaceae) é uma planta largamente utilizada em regiöes tropicais e subtropciais como medicaçäo tópica em afecçöes cutäneas de natureza alérgica. Tal utilizaçäo foi fundamentada sob o ponto de vista farmacológico, por um trabalho (NASSIS, 1991) que demonstra ser o suco extraído das folhas desta planta, um potente antagonista dos receptores H1 a nível periférico em ratos. Durante a realizaçäo do referido trabalho, foi verificada uma aparente açäo depressora central exercida pelo suco caracterizada por sonolência e imobilidade dos animais. No presente trabalho, a proposta foi estudar tal açäo, verificando se realmente o suco exercia açäo depressora significativa sobre o SNC. Os experimentos realizados demonstraram que o suco (4,0g/Kg) inibe a atividade locomotora em campo aberto, e potência o tempo de sono induzido por pentobarbital em ratos. Resultados similares foram obtidos com a administraçäo de difenidramina (20mg/Kg), indicando a necessidade de realizaçäo de experimentos mais especificos para a verificaçäo de uma eventual açäo anti-histamínina central

Drug interaction of promethazine & other non-conventional antimicrobial chemotherapeutic agents.

The antihistamine compound promethazine (Pz) showed significant antibacterial action when tested against 124 strains of aerobic and 13 strains of anaerobic bacteria belonging to both Gram positive and Gram negative genera. The range of MIC (micrograms/ml) of Pz varied between 50 and 200 micrograms/ml among most of the test organisms. Six Pz-sensitive strains were found to be simultaneously sensitive to similar non-conventional antimicrobics, e.g., methdilazine, bromodiphenhydramine, diphenhydramine, methyl-DOPA, promazine and the antibiotic augmentin. A high degree of synergism was observed in vitro when Pz was used in combination with methdilazine and bromodiphenhydramine.

Effects of prenatal diphenhydramine administration on sexual behavior in rats

In order to study the involvement of the brain histamine system on the sexual vehavior of rats prenatally exposed to the histamine H1 receptor blockader, diphenhydramine (DPD), the famale lordotic response and male sexual behavior were aalyzed. The results show that the lorditic response in the prenatal DPD-treated rats was increased in relation to control animals. Impairment of male sexual behavior was indicated by an invrease in ejaculation latency, in the number of mounts and a decrease in the number of ejaculations up to 30 min after the first intromission. Prenatal expossure to DPD thus appears to alter female and male sexual behavior on reaching adulthood

Effect of some antihistaminic drugs on the oestrous cycyle of rats.

The effect of some antihistaminic drugs namely antazoline hydrochloride, diphenhy, dramine hydrochloride and mepyramine maleate has been investigated on the oestrous cycle in albino rats. On daily intraperitoneal administration, for 6 days, all the three drugs (10 mg/kg) significantly (P less than 0.001) prolonged the duration of oestrous cycle. The duration of subsequent cycle returned to near normal.