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 were determined under the same experimental conditions. 2. Buspirone, gepirone, 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 administration (i.p.), their ED(50) values were: buspirone, 134 mu g/kg; ipsapirone, 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 similar chemical structure that binds to the 5-HT1A receptor, most likely it is ''N-C-C-C-C-N'' aliphatic backbone. 5. Buspirone and tandospirone required 4 or more min to totally block the spontaneous activity, while gepirone and ipsapirone blocked it in 3 min. 6. The dose-response curves from buspirone and tandospirone demonstrated enough dissimilarity to the dose-response curves from gepirone and ipsapirone to suggest differences in their rates of absorption, and/or differences in the production of active and inactive metabolites.