The effect of long-term treatment with amine-depleting drugs or chlorpromazine on alpha-adrenoreceptors and 5-HT2 receptors in the brain of the rat.

The effect of chlorpromazine, oxypertine, tetrabenazine or reserpine on alpha-adrenoreceptors and 5-HT2 receptors in the brain of the rat was studied both in vitro and after the administration to animals for up to 12 months. In vitro, chlorpromazine and oxypertine potently displaced the specific binding of [3H]WB 4101 to alpha 1 adrenoreceptors in the cortex and of [3H]ketanserin to 5-HT2 receptors in the frontal cortex. Both drugs were moderately effective in displacing the specific binding of [3H]clonidine from cortical alpha 2-adrenoreceptors. Tetrabenazine only weakly displaced the specific binding of [3H]WB 4101, [3H] clonidine and [3H]ketanserin. The incorporation of reserpine into tissue incubates had little effect on the binding of any of these ligands. Administration of chlorpromazine (33-36 mg/kg/day) to rats for up to 12 months reduced the number of specific binding sites (Bmax) for [3H]ketanserin in the frontal cortex, but did not alter the specific binding of [3H]WB 4101 or specific [3H]clonidine to cortical membranes. In contrast, treatment with oxypertine (6.3-7.3 mg/kg/day), tetrabenazine (6.0-6.7 mg/kg/day) or reserpine (0.28-0.30 mg/kg/day) increased the Bmax for the specific binding of [3H]WB 4101, but did not alter the specific binding of [3H]clonidine or [3H]ketanserin. Oxypertine resembles chlorpromazine in its ability to interact with alpha-adrenoreceptors and 5-HT2 receptors in brain. Tetrabenazine and reserpine have few direct actions on post-synaptic monoamine receptors. However, on long-term administration, oxypertine, like tetrabenazine and reserpine, predominantly altered alpha 1-adrenoreceptors, whereas chlorpromazine influenced the population of 5-HT2 receptors.