Characteristics of the Inhibition of Ligand Binding to Serotonin Receptors in Rat Brain Membranes by Verapamil

Abstract

Characteristics of the interaction of verapamil with serotonin receptors were studied in rat brain membranes using a radioligand binding technique. While verapamil competed for the [³H]ketanserin binding sites at low concentrations with the K_i value of 0.41 μM, much higher concentrations were needed to inhibit the binding of [³H]serotonin to its binding sites, indicating higher affinity of verapamil binding for 5-HT₂ than 5-HT₁ receptors. The inhibitory action of verapamil on the [³H]ketanserin binding was stereoselective; the (-)isomer was about ten times more potent than the (+)isomer. The interaction of verapamil with [³H]ketanserin was competitive and reversible. While D600, a verapamil derivative, also competed for the [³H]ketanserin binding sites, nifedipine and nicardipine had practically no ability to inhibit the ligand binding to 5-HT₁ or 5-HT₂ receptors. Although diltiazem competed for 5-HT₂ receptors, the affinity was much less than verapamil and D600.