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Anticonflict effects of the 5-HT1A compound flesinoxan

Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA

S. Gleeson

Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA

M.A. Nader

Department of Psychiatry, University of Chicago, Chicago, Illinois 60637, USA

S.M. Hoffmann

Department of Psychiatry, University of Chicago, Chicago, Illinois 60637, USA

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.

Journal of Psychopharmacology, Vol. 3, No. 2, 64-69 (1989)
DOI: 10.1177/026988118900300203


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