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>In‐Vivo Pharmacological Studies of 2‐N‐Carboxamidinonormianserin, a Histamine and 5‐Hydroxytryptamine Antagonist Lacking Central Effects
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In‐Vivo Pharmacological Studies of 2‐N‐Carboxamidinonormianserin, a Histamine and 5‐Hydroxytryptamine Antagonist Lacking Central Effects
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机译：In‐Vivo Pharmacological Studies of 2‐N‐Carboxamidinonormianserin, a Histamine and 5‐Hydroxytryptamine Antagonist Lacking Central Effects
Abstract—The in‐vivo pharmacological properties have been examined of FCC5 (2‐N‐carboxamidino‐1, 2, 3, 4, 10, 14b‐hexahydrodibenzo (c.f.) pyrazino (1, 2‐α)azepine hydrochloride), a guanidino analogue of mianserin. FCC5 (30–100 μg kg−1, i.v.) caused long‐lasting (>1 h) attenuation of histamine‐ and 5‐hydroxytryptamine (5‐HT)‐induced bronchoconstriction in the anaesthetized guinea‐pig. FCC5 (≤lmg kg−1, i.v.) had no effect on submaximal bronchoconstrictor responses caused by i.v. acetylcholine or the thromboxane A2‐mimetic U46619 ((15S)‐hydroxy‐11α,9α‐(epoxymethano)prosta‐5Z,13E‐dienoic acid). The pressor effects of 5‐HT in anaesthetized and pithed rats were inhibited by FCC5 (0·3–1·0 mg kg−1, i.v.). Higher doses of FCC5 (3 mg kg−1, i.v.) reduced bradycardia and depressor responses to 5‐HT in anaesthetized rats. In anaesthetized cats and rats and also pithed rats, FCC5 (0·1–1·0 mg kg−1, i.v.) caused sympathomimetic effects as demonstrated by pressor responses and tachycardia. FCC5 (0·1–0·3 mg kg−1, i.v.) inhibited pressor responses to tyramine whereas those to noradrenaline and sympathetic nerve stimulation were potentiated. Oedema in the rat paw caused by intraplantar 5‐HT was inhibited by FCC5 (ID50 0·76 mg kg−1, i.p.; and 2·7 mg kg−1, p.o.). In decerebrate rats which had been spinalized at T6–8, fenfluramine‐induced facilitation of the flexor reflex of the anterior tibialis muscle was inhibited by mianserin (ID50 0·36 mg kg−1, i.p.) but not by FCC5 (≤3mg kg−1, i.p.). Head twitches in carbidopapretreated mice induced byl‐5‐hydroxytryptophan were inhibited by mianserin (ID50 0·11 mg kg−1, i.p.), but not by FCC5 (≤30 mg kg−1, i.p.). It is concluded that FCC5 possesses an
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