title: The pre- and postjunctional activity of CP-122,288, a conformationally restricted analogue of sumatriptan.
abstract: The present study investigated the pre- and postjunctional of CP-122,288 (5-methyl-aminosulphonylmethyl-3-(N-methylpyrrolidin-2R-yl-m ethyl)-1H-indole), an analogue of the vascular 5-HT1 receptor agonist, sumatriptan. CP-122,288 inhibited neurogenic plasma protein extravasation in rat dura with a potency approximately 40,000-fold greater than sumatriptan (ID50 values of 0.3 pmol/kg and 13.9 nmol/kg i.v. respectively). However, CP-122,288 was only approximately 2-fold more potent than sumatriptan at inhibiting neurogenically mediated contractions of the dog saphenous vein. CP-122,288 contracted the dog saphenous vein and basilar artery with a potency approximately 2-fold greater than that of sumatriptan. Both compounds possessed similar affinities at either human 5-HT1D alpha or 5-HT1D beta receptors. It is concluded that CP-122,288 exhibits a prejunctional selectivity in the meninges to inhibit dural plasma protein extravasation independent of 5-HT1D alpha and 5-HT1D beta receptor activation.
authors.affiliation: Glaxo Research and Development Ltd., Herts, UK.
authors.forename: D T
authors.initials: DT
authors.lastname: Beattie
authors.forename: H E
authors.initials: HE
authors.lastname: Connor
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000294:innervation; D001798:Blood Proteins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002460:Cell Line; D004285:Dogs; D004388:Dura Mater / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000882:Haplorhini; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation; D009469:Neuromuscular Junction / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects / Q000294:innervation; D018170:Sumatriptan / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D011759:Pyrrolidines; D011985:Receptors, Serotonin; C085263:CP 122288; D018170:Sumatriptan