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• W158148919 abstract "The antihypertensive effects of a new transdermal delivery system for clonidine (CAS 4205-90-7, clonidine tape, M-5041T) were investigated in spontaneously hypertensive rats (SHR), 2-kidney, 1-clip renal hypertensive rats (RHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. M-5041T (0.5-4.5 mg/kg) elicited a long-lasting hypotensive effect that was accompanied by bradycardia in a dose-dependent manner during 24-h patching on the backs of rats in all three hypertensive rat models. The hypotensive effect of M-5041T was more persistent than that of oral administration of clonidine (50 and 100 micrograms/kg) in both SHR and RHR. The most pronounced hypotensive effect of M-5041T was observed in DOCA-salt hypertensive rats. Plasma clonidine concentrations following transdermal application of M-5041T (1.5 mg/kg) were approximately 2-3 fold higher in DOCA-salt hypertensive rats compared with SHR. Electrical conductance of the skin surface, an index of the water content of the stratum corneum, was greater in DOCA-salt hypertensive rats than in SHR, suggesting that the delivery of clonidine may have been enhanced as a result of an increase in skin permeability due to the increase in water content of the stratum corneum in DOCA-salt hypertensive rats. Co-administration of M-5041T (0.5 mg/kg) with either trichloromethiazide (1 mg/kg, orally) or nifedipine (3 mg/kg, orally) at each sub-dose which affected both systolic blood pressure and heart rate produced significant hypotensive and bradycardic effects in SHR. Following repeated daily applications of M-5041T (1.5 mg/kg) for 7 consecutive days in SHR, significant hypotensive and bradycardic effects were produced at 6 h post-patching and then disappeared at 24 h post-patching in each trial. The plasma clonidine concentrations at 6 and 24 h post-patching were similar from the first to the seventh trial. No significant changes in blood pressure and heart rate were observed after termination of the regimen. These findings suggest that M-5041T could serve as an efficient and useful antihypertensive transdermal delivery system in humans without producing tolerance to the hypotensive effect and withdrawal syndrome after abrupt cessation of the treatment when used alone or with either a diuretic or a calcium channel blocker." @default.
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• W158148919 date "1996-03-01" @default.
• W158148919 modified "2023-09-23" @default.
• W158148919 title "Antihypertensive effects of a new transdermal delivery system for clonidine in genetic and experimental hypertensive rats." @default.
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