Conformationally restricted sumatriptan analogues, CP-122,288 and CP-122,638 exhibit enhanced potency against neurogenic inflammation in dura mater.
CP-122,288 and CP-122,638 blocked plasma protein extravasation response within dura mater following trigeminal ganglion stimulation. The threshold (1 and 0.1 pmol/kg, respectively) was remarkably lower than for sumatriptan (7 nmol/kg), as was the dose at maximum response. As with sumatriptan, substance P-induced plasma leakage was unaffected by either compound, and metergoline only partially (27%) reversed the effects of CP-122,288. The data suggest the importance of modifications at the aminoethyl side chain to the actions of sumatriptan and possibly to the treatment of migraine headache.
Lee
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WS
Stroke Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Moskowitz
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MA
D000818:Animals; D004388:Dura Mater / Q000187:drug effects* / Q000473:pathology; D004558:Electric Stimulation; D006168:Guinea Pigs; D008297:Male; D008581:Meningitis / Q000188:drug therapy* / Q000473:pathology; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D018170:Sumatriptan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000502:physiology
D011759:Pyrrolidines; C085263:CP 122288; C085264:CP 122638; D018170:Sumatriptan