title: The effects of 5-HT1A, 5-HT1B and 5-HT1D receptor agonists on trigeminal nociceptive neurotransmission in anaesthetized rats.
abstract: Pre-clinical studies have suggested that one mechanism of antimigraine action of the 'triptan' 5-HT1B/1D receptor agonists may be through inhibition of central nociceptive transmission in the trigeminal dorsal horn. In anaesthetized rats, the 5-HT1B/1D receptor agonist, zolmitriptan (up to 3 mg kg(-1), i.v.), inhibited the action potential discharge of single trigeminal neurones to noxious electrical stimulation of the middle meningeal artery. In contrast, the selective 5-HT1B receptor agonist, CP-93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one), and the 5-HT1A receptor selective agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) had no effect in this assay at up to 3 mg kg(-1), i.v.. Brain penetrant, triptan 5-HT1B/1D receptor agonists may therefore mediate their central trigeminal anti-nociceptive action in the rat via 5-HT1D, but not 5-HT1B or 5-HT1A, receptors.
authors.affiliation: Merck Sharp and Dohme Research Laboratories, Neuroscience Research Center, Harlow, Essex, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cumberbatch
authors.forename: R G
authors.initials: RG
authors.lastname: Hill
authors.forename: R J
authors.initials: RJ
authors.lastname: Hargreaves
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy; D010080:Oxazoles / Q000494:pharmacology*; D023303:Oxazolidinones; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects*; D014363:Tryptamines
chemical_list: D000700:Analgesics; D010080:Oxazoles; D023303:Oxazolidinones; D011725:Pyridines; D011758:Pyrroles; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; C089750:zolmitriptan; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin