Biochemical and pharmacological properties of SR 46349B, a new potent and selective 5-hydroxytryptamine2 receptor antagonist

摘要: A new potent, selective and p.o. active serotonergic [5-hydroxytryptamine (5-HT2)] receptor antagonist, SR 46349B [trans, 4-([3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-flurophenyl++ +)propen-1-yl]phenol hemifumarate) has been characterized by a series of "in vitro" vivo" methods. Based upon binding studies with 5-HT2 receptors in rat brain cortical membranes blockade 5-HT-induced contractions isolated tissues (rabbit thoracic aorta, jugular vein, caudal artery, uterus guinea pig trachea), showed high affinity for receptors. Furthermore, displayed moderate the 5-HT1C had no other 5-HT1 subclass (5-HT1A, 5-HT1B or 5-HT1D), dopamine (D1 D2), "alpha" adrenergic (alpha-1 alpha-2), sodium calcium channel histamine (H1) It did not interact (H1), alpha-1 5-HT3 smooth muscle preparations. No inhibition uptake norepinephrine, 5-HT was seen. pressor responses to pithed rats vivo mice, found be potent antagonist relatively long duration action. Behavioral experiments, including mescaline- 5-hydroxytryptophan-induced head twitches learned helplessness, as well sleep-waking cycle EEG spectral parameter studies, indicated that classical psychopharmacological profile.