Central and peripheral effects of S 3341 [(N-dicyclopropylmethyl)-amino-2-oxazoline] in animal models.
The effects on blood pressure and heart rate of S 3341 [(N-dicyclopropylmethyl)-amino-2-oxazoline] were investigated in rats and cats. Upon i.v. injection in pithed rats, S 3341 produced pressor responses which were antagonized by prazosin as well as by yohimbine. In pentobarbitone-anesthetized rats S 3341 produced a short-lasting increase in mean arterial pressure, followed by a long-lasting reduction. During a 12-day, continuous subcutaneous infusion in conscious spontaneously hypertensive rats, S 3341 reduced blood pressure and heart rate. Upon cessation of treatment, an overshoot of heart rate and blood pressure lability occurred. The hypotensive effect was abolished by reserpinization of the rats. S 3341 was more potent in reducing mean arterial pressure upon infusion via the vertebral artery than after infusion via the femoral artery of chloralose-anesthetized cats. S 3341 did not prolong the hexobarbitone-induced loss of righting reflex in mice. S 3341 was more potent in displacing [3H]clonidine than [3H]prazosin from their specific binding sites in rat brain membranes. These data characterize S 3341 as a clonidine-like, centrally acting antihypertensive drug. The lack of sedative effect, as assessed by the prolongation of hexobarbitone-induced sleeping in mice, remains to be clarified.
van Zwieten
P A
PA
Thoolen
M J
MJ
Jonkman
F A
FA
Wilffert
B
B
de Jonge
A
A
Timmermans
P B
PB
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002415:Cats; D003000:Clonidine / Q000378:metabolism; D003655:Decerebrate State; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006591:Hexobarbital / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D000077769:Rilmenidine; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D010080:Oxazoles; D006591:Hexobarbital; D003000:Clonidine; D000077769:Rilmenidine; D011224:Prazosin