Imipramine and tetrabenazine: effects on monoamine receptor binding sites and phosphoinositide hydrolysis.
Treatment of rats for 21 days with tetrabenazine, a drug which depletes monoamines and is used behaviorally to screen for antidepressants, significantly decreased 5-HT2 receptor density, increased alpha 1-adrenoceptor density but did not alter beta-adrenoceptor density in homogenates of frontal cortices labeled with [3H]ketanserin, [3H]prazosin and [3H]dihydroalprenolol, respectively. These effects were not opposite to those of the antidepressant drug imipramine which decreased both 5-HT2 and beta-adrenoceptor density and did not alter alpha 1-adrenoceptor density. Some evidence for antagonistic interactions between the two drugs was found in that imipramine partially prevented the tetrabenazine-induced increase in alpha 1-adrenoceptor density and tetrabenazine partially prevented the imipramine-induced decrease in beta-adrenoceptor density. Neither drug altered phosphoinositide hydrolysis coupled to alpha 1-adrenoceptors. While the effects of tetrabenazine are frequently attributed to its reserpine-like action of depleting monoamines, these results provide the first indication that tetrabenazine alters 5-HT2 and beta-adrenoceptor density in a manner different from that of reserpine.
Butler
P D
PD
New York State Psychiatric Institute, NY.
Edwards
E
E
Barkai
A I
AI
D000818:Animals; D004082:Dihydroalprenolol; D006868:Hydrolysis; D007099:Imipramine / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007650:Ketanserin; D007700:Kinetics; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D011224:Prazosin; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D013747:Tetrabenazine / Q000494:pharmacology*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011941:Receptors, Adrenergic; D011985:Receptors, Serotonin; D004082:Dihydroalprenolol; D007650:Ketanserin; D007099:Imipramine; D011224:Prazosin; D013747:Tetrabenazine