ANTAGONISTIC ACTIVITY OF SOME PHENOTHIAZINE DERIVATIVES AGAINST NEUROHUMORAL TRANSMITTERS

[摘要] References(18)Cited-By(6)The antagonistic activity of eighteen phenothiazine derivatives against the neurohumors histamine, ACh, NA and 5-HT was studied in vitro and compared with accepted specific antagonists, viz., diphenhydramine, atropine, tubocurarine, phenoxybenzamine and LSD-25. The phenothiazines exhibited a dual antagonism (competitive and non-competitive) against histamine and muscarinic action of ACh. Many of them appeared more potent and more specific on histamine receptors than on ACh receptors while several others did not discriminate between the two receptor types. The phenothiazines showed a non-competitive antagonism against ACh (nicotinic action), NA and 5-HT. The activity against ACh (nicotinic action) was low while that against 5-HT was moderate. The α-adrenergic blocking activity was not shared by all the derivatives and some even potentiated the NA response. Only atropine and tubocurarine exhibited a pure competitive antagonism over a wide concentration range on the muscarinic and nicotinic receptors, respectively. Phenoxybenzamine possessed the widest spectrum of activity, antagonizing all the neuro humors. 5-HT receptors showed the maximum susceptibility to blockade, reacting to all the phenothiazines and reference antagonists.

[学科分类] 药理学