Antimigraine drug interactions with serotonin receptor subtypes in human brain

The interactions of antimigraine agents with serotonin (5‐hydroxytryptamine, 5‐HT) receptor subtypes were analyzed in human frontal cortex membranes. The drugs studied included 5‐HT antagonists, beta‐adrenergic antagonists, and calcium channel blockers. At 5‐HT 1A sites labeled by 3 H‐8‐hydroxy‐2‐(N, N‐dipropylamino)‐tetralin, (–)pindolol, alprenolol, (–)propranolol, methysergide, cyproheptadine, and pizotifen are similar in that they display affinities of approximately 100 nM for this receptor. By contrast, only methysergide displays relatively high affinity (120 ± 60 nM), whereas all other drugs have affinities greater than 1,000 nM for non‐5‐HT 1A sites labeled by 3 H‐5‐HT in human cortex. Finally, at 5‐HT 2 receptors labeled by 3 H‐spiperone, cyproheptadine, methysergide, and pizotifen are extremely potent agents (affinity constants of 1 to 10 nM), whereas amitriptyline (23 ± 4 nM), verapamil (140 ± 50 nM), and nifedipine (320 ± 80 nM) are moderately potent. All other drugs are inactive at concentrations below 1,000 nM. These data demonstrate that most antimigraine drugs display high affinity for the 5‐HT 1A and/or 5‐HT 2 receptor subtypes in human brain. However, antimigraine efficacy cannot be explained by drug interactions with a single 5‐HT receptor subtype.