Anticonflict effects of the 5-HT1A compound flesinoxan.

The new phenylpiperazine derivative flesinoxan, a potent and selective serotonin(1A) (5-HT(1A)) agonist, was examined under a procedure that has proved to be a reliable and sensitive method for detecting novel anxiolytic drugs believed to produce their effects at the 5-HT( 1A) receptor subtype. Key pecking by pigeons was maintained by the presentation of food following every 30th response in the presence of a white keylight; during an alternate component, correlated with a red keylight, every 30th response produced food and electric shock which suppressed responding (punishment). Flesinoxan doses from 0.001 to 0.3 mg/ kg, intramuscularly, produced significant increases in punished responding at doses that did not affect unpunished responding. Doses of flesinoxan between 1.0 and 3.0 mg/kg also increased punished responding but produced decreases in responding that was not punished. In a second study flesinoxan substituted for the 5-HT(1A) anxiolytic buspirone under a drug discrimination procedure, providing further evidence that the behavioural effects offlesinoxan are mediated by 5-HT(1A) mechanisms. Based on these findings, it would appear that flesinoxan should be a useful compound in the clinical management of anxiety.