THE EFFECTS OF AZAPIRONES ON SEROTONIN(1A) NEURONS OF THE DORSAL RAPHE

1. The effects of buspirone, gepirone, ipsapirone and tandospirone on spontaneously discharging serotonergic neurons of the dorsal raphe wer e determined under the same experimental conditions. 2. Buspirone, gep irone, ipsapirone and tandospirone were equally efficacious and acted in a dose-dependent manner to totally inhibit the spontaneous activity of serotonergic neurons. 3. Based on their effects six min after admi nistration (i.p.), their ED(50) values were: buspirone, 134 mu g/kg; i psapirone, 220 mu g/kg; gepirone, 225 mu g/kg; tandospirone, 198 mu g/ kg. 4. The similarity of these ED(50) data suggest that they share a s imilar chemical structure that binds to the 5-HT1A receptor, most like ly it is ''N-C-C-C-C-N'' aliphatic backbone. 5. Buspirone and tandospi rone required 4 or more min to totally block the spontaneous activity, while gepirone and ipsapirone blocked it in 3 min. 6. The dose-respon se curves from buspirone and tandospirone demonstrated enough dissimil arity to the dose-response curves from gepirone and ipsapirone to sugg est differences in their rates of absorption, and/or differences in th e production of active and inactive metabolites.