The effects of azapirones on serotonin1A 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 ED50 values were: buspirone, 134 micrograms/kg; ipsapirone, 220 micrograms/kg; gepirone, 225 micrograms/kg; tandospirone, 198 micrograms/kg. 4. The similarity of these ED50 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.
Matheson
G K
GK
Neurobiology Laboratory, Indiana University, School of Medicine, Evansville 47714.
Pfeifer
D M
DM
Weiberg
M B
MB
Michel
C
C
D000818:Animals; D002065:Buspirone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D054833:Isoindoles; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C055267:tandospirone; C043077:ipsapirone; C039979:gepirone; D002065:Buspirone