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-HT1A sites labeled by 3H-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-HT1A sites labeled by 3H-5-HT in human cortex. Finally, at 5-HT2 receptors labeled by 3H-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-HT1A and/or 5-HT2 receptor subtypes in human brain. However, antimigraine efficacy cannot be explained by drug interactions with a single 5-HT receptor subtype.
D000319:Adrenergic beta-Antagonists / Q000378:metabolism* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000627:therapeutic use; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism* / Q000627:therapeutic use; D013134:Spiperone / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013134:Spiperone