TY - JOUR
T1 - 6-[N,S-dimethyl-N'-cyanothioureidomethyl]-6,11-dihydro-5H-dibenz[b,e]a zepine hydrochloride (Fran 12)
T2 - A histamine and 5-hydroxytryptamine antagonist with pressor properties
AU - Law, S. C.
AU - Guyett, F. J.
AU - King, R. G.
AU - Boura, A. L A
AU - Jackson, W. R.
AU - Hodgson, W. C.
PY - 1992/1/1
Y1 - 1992/1/1
N2 - We have synthesized and examined some of the pharmacological properties of 6-[N,S-dimethyl-N'-cyanoisothioureidomethyl]-6,11-dihydro-5H-dibenz(b, e)azepine hydrochloride (Fran 12), a derivative of 6-methylaminomethyl-6,11-dihydro-5H-dibenz[b,e,]azepine. In the guinea-pig isolated ileum, Fran 12 (10-7-10-5 M) caused parallel rightward shifts of the concentration-response curves to histamine. A Schild plot gave a pA2 of 7.48, with a slope not significantly different from -1.0. In the rat stomach fundus strip and in endothelium-denuded aortic rings, Fran 12 inhibited contractile responses to 5-hydroxytryptamine in a noncompetitive manner. In both chloralose-anaesthetized and pithed rats, it inhibited pressor responses to 5-hydroxytryptamine. It had no effect on depressor responses to 5-hydroxytryptamine in anaesthetized rats. In pithed rats, Fran 12 (0.25-2 mg/kg, i.v.) produced dose-dependent increases in blood pressure. These were not inhibited by i.v. phentolamine, prazosin, yohimbine, propranolol, methysergide, pentolinium or atropine but were inhibited by verapamil. These results indicate that Fran 12 is a histamine and 5-hydroxytryptamine antagonist which also exerts pressor effects via a peripheral action. The pressor action does not appear to be mediated via effects on α1- or α2-adrenoceptors, muscarinic or nicotinic cholinoceptors or 5-hydroxytryptamine receptors, although calcium channel activation may play a role.
AB - We have synthesized and examined some of the pharmacological properties of 6-[N,S-dimethyl-N'-cyanoisothioureidomethyl]-6,11-dihydro-5H-dibenz(b, e)azepine hydrochloride (Fran 12), a derivative of 6-methylaminomethyl-6,11-dihydro-5H-dibenz[b,e,]azepine. In the guinea-pig isolated ileum, Fran 12 (10-7-10-5 M) caused parallel rightward shifts of the concentration-response curves to histamine. A Schild plot gave a pA2 of 7.48, with a slope not significantly different from -1.0. In the rat stomach fundus strip and in endothelium-denuded aortic rings, Fran 12 inhibited contractile responses to 5-hydroxytryptamine in a noncompetitive manner. In both chloralose-anaesthetized and pithed rats, it inhibited pressor responses to 5-hydroxytryptamine. It had no effect on depressor responses to 5-hydroxytryptamine in anaesthetized rats. In pithed rats, Fran 12 (0.25-2 mg/kg, i.v.) produced dose-dependent increases in blood pressure. These were not inhibited by i.v. phentolamine, prazosin, yohimbine, propranolol, methysergide, pentolinium or atropine but were inhibited by verapamil. These results indicate that Fran 12 is a histamine and 5-hydroxytryptamine antagonist which also exerts pressor effects via a peripheral action. The pressor action does not appear to be mediated via effects on α1- or α2-adrenoceptors, muscarinic or nicotinic cholinoceptors or 5-hydroxytryptamine receptors, although calcium channel activation may play a role.
UR - http://www.scopus.com/inward/record.url?scp=0026686583&partnerID=8YFLogxK
M3 - Article
C2 - 1360792
AN - SCOPUS:0026686583
SN - 0003-9780
VL - 317
SP - 67
EP - 80
JO - Archives Internationales de Pharmacodynamie et de Therapie
JF - Archives Internationales de Pharmacodynamie et de Therapie
ER -