Conformationally restricted sumatriptan analogues, CP-122,288 and CP-122,638 exhibit enhanced potency against neurogenic inflammation in dura mater.

Abstract

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.

• Authors: W S Lee, M A Moskowitz
• Journal: Brain research (Brain Res) Vol. 626 Issue 1-2 Pg. 303-5 (Oct 29 1993) ISSN: 0006-8993 [Print] Netherlands
• PMID: 8281439 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Pyrrolidines
• CP 122288
• CP 122638
• Sumatriptan

Topics

• Animals
• Dura Mater (drug effects, pathology)
• Electric Stimulation
• Guinea Pigs
• Male
• Meningitis (drug therapy, pathology)
• Molecular Conformation
• Pyrrolidines (chemistry, pharmacology)
• Sumatriptan (analogs & derivatives, chemistry, pharmacology)
• Trigeminal Ganglion (physiology)