Decreased 5-HT2 but not 5-HT1 receptor binding in cortex of rat after chronic administration of dothiepin. Application of the Woolf plot to analysis of binding parameters.
Prolonged administration of the antidepressant drug, dothiepin hydrochloride (30 mg/kg orally twice daily for 24 days), resulted in a significant decrease in the population of serotonin2 (5-HT2) binding sites in the frontal cortex of rats whereas serotonin1 (5-HT1) binding sites remained unaltered. No significant differences in affinity constants for either ligand-binding site interaction were observed. Analyses of the binding parameters was performed using linear transformation methods of the specific binding isotherms according to Scatchard (1949) [Ann. N.Y. Acad. Sci. 51: 660-672] or Woolf (see Haldane, 1957: Nature 179: 832). The resulting parameter estimates generated in each analysis were compared. Although both methods demonstrated the decreased Bmax for 5-HT2 binding sites with no change in 5-HT1 sites after prolonged administration of dothiepin, Woolf analyses gave reliably better estimates of the binding parameters as judged by examination of the respective correlation coefficients for best fit linear regression lines.
D000818:Animals; D002540:Cerebral Cortex / Q000032:analysis / Q000187:drug effects*; D003988:Dibenzothiepins / Q000494:pharmacology*; D004308:Dothiepin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects*
D003988:Dibenzothiepins; D011985:Receptors, Serotonin; D004308:Dothiepin