Hypotensive and bradycardic effects of dl-tetrahydropalmatine mediated by decrease in hypothalamic serotonin release in the rat.

In anesthetized rats, intravenous administration of dl-tetrahydropalmatine (dl-THP, 1-10 mg/kg) elicited proportional hypotension, bradycardia and decreases in hypothalamic serotonin (5-HT) release (measured by carbon-fiber electrodes in combination with voltammetry). In addition, postsynaptic blockade of 5-HT2 receptors with cyproheptadine (2-5 mg/kg, i.v.) or ketanserin (2-5 mg/kg, i.v.) produced both hypotension and bradycardia, while stimulation of 5-HT2 receptors with 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10-250 mg/kg, i.v.) produced both hypertension and tachycardia. The dl-THP-induced hypotension and bradycardia could be reversed by DOI treatment. The data indicate that dl-THP decreases both arterial pressure and heart rate through a serotonergic release process in the hypothalamus.