The in vivo pharmacological profile of a 5-HT1 receptor agonist, CP-122,288, a selective inhibitor of neurogenic inflammation

British Journal of Pharmacology
P GuptaN B Shepperson

Abstract

1. The aim of the present study was to investigate the in vivo pharmacological profile of CP-122,288, an indole-derivative with a conformationally restricted N-methylpyrrolidinyl basic side chain in the C-3 position. This C-3 substituent structurally differentiates CP-122,288 from the 5-HT1D receptor agonist sumatriptan, which possesses an N,N-dimethylaminoethyl group. [Formula: see text] 2. When administered prior to electrical stimulation of the trigeminal ganglion, CP-122,288 (0.3-300 ng kg-1, i.v.) produced a dose-related inhibition of plasma protein extravasation in rat dura mater (minimum effective dose, MED, 3 ng kg-1 i.v., P < 0.05; maximal inhibition of plasma extravasation at 30 ng kg-1 i.v., P < 0.01). Sumatriptan produced a similar inhibition of plasma leakage in the dura, but at much higher dose levels (MED, 100 micrograms kg-1 i.v., P < 0.05). Thus, CP-122,288 is of the order of 10(4) fold more potent than sumatriptan. 3. At all doses tested, CP-122,288 did not inhibit plasma protein extravasation measured in extracranial tissues such as the lower lip, eyelid, and conjunctiva. 4. In a separate series of studies in the anaesthetized rat, CP-122,288 (0.003-3 micrograms kg-1 i.v.) produced no change in either heart r...Continue Reading

References

May 30, 1992·BMJ : British Medical Journal·F WillettM Armitage
Aug 1, 1992·Trends in Pharmacological Sciences·M A Moskowitz
Nov 1, 1992·Naunyn-Schmiedeberg's Archives of Pharmacology·A A ParsonsA J Kaumann
Dec 1, 1991·Trends in Pharmacological Sciences·P P Humphrey, W Feniuk
Jan 1, 1989·British Journal of Pharmacology·W FeniukM J Perren
Feb 14, 1989·European Journal of Pharmacology·H E ConnorP P Humphrey
Jan 1, 1994·European Neurology·A J Pilgrim
Apr 3, 1993·Lancet·J P OttervangerB H Stricker
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·G W RebeckM A Moskowitz

❮ Previous
Next ❯

Citations

Aug 19, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Carlos M Villalón, David Centurión
Jun 5, 1997·European Journal of Pharmacology·D J WilliamsonR J Hargreaves
Jun 28, 2000·Progress in Neurobiology·P J Goadsby
Feb 13, 1999·Progress in Neurobiology·M J Millan
Oct 31, 2002·Human Psychopharmacology·Marie NaughtonBrian E. Leonard
Aug 21, 2013·Expert Review of Neurotherapeutics·Simon Akerman, Marcela Romero-Reyes
Jan 24, 2006·Progress in Neuro-psychopharmacology & Biological Psychiatry·Mostafa El Mansari, Pierre Blier

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Electrophysiology

Cardiac electrophysiology is the study of electrical activities of the heart and includes the assessment, diagnosis, and treatment of cardiac events. Find the latest research on cardiac electrophysiology here.