5-HT1 and 5-HT2 Binding Characteristics of Some Quipazine Analogues

Article abstract of DOI:10.1021/jm00161a038

Arylpiperazines, such as 1-(3-trifluoromethylphenyl)piperazine (TFMPP) and its chloro analogue mCPP, are 5-HT₁ agonists, whereas quipazine, i.e., 2-(1-piperazino)quinoline, appears to be a 5-HT₂ agonist.Radioligand binding studies using rat cortical membrane homogenates and drug discrimination studies using rats trained to discriminate a 5-HT₁ agonist (i.e., TFMPP) or a 5-HT₂ agonist (i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline reveal that quipazine and its 1-deaza analogue 2-naphthylpiperazine (2-NP) bind at 5-HT₁ and 5-HT₂ sites but produce stimulus effects similar to those of DOM.A structurally related compound, 1-naphthylpiperazine (1-NP), possesses a high affinity for 5-HT₁ (K_i = 5 nM) and 5-HT₂ (K_i = 18 nM) sites. 1-NP produces stimulus effects similar to those of TFMPP and is able to antagonize the stimulus effects produced by DOM.The present results suggest that the unsubstituted benzene ring of quipazine, and of its 1-deaza analogue 2-naphthylpiperazine, makes a significant contribution to the binding of these agents to 5-HT₂ sites and, more importantly, may account for their 5-HT₂ agonist properties.