Neurogenic dural protein extravasation induced by meta-chlorophenylpiperazine (mCPP) involves nitric oxide and 5-HT2B receptor activation.

Abstract

The compound m-chlorophenylpiperazine (mCPP), which is known to trigger migraine-like head pain in some subjects, was evaluated for its ability to induce dural plasma protein extravasation (PPE) in guinea pigs. Intravenous mCPP dose-dependently increased PPE. This effect was inhibited by non-selective 5-HT2 receptor antagonists (methysergide, LY53857, LY215840), by a peripherally restricted 5-HT2 receptor antagonist (xylamidine) and by a 5-HT2B selective receptor antagonist (LY202146). These data suggests that peripheral 5-HT2B receptors mediate mCPP-induced PPE. The nitric oxide synthase inhibitor L-NAME and 5-HT1 agonist sumatriptan also blocked mCPP-induced PPE, suggesting a role for nitric oxide (NO) and the trigeminal system, respectively. NO release has been linked to activation of the 5-HT2B receptor on the vascular endothelium. However, LY202146 did not block PPE induced by electrical stimulation of the trigeminal ganglion. These data are consistent with activation of peripheral 5-HT2B receptors initiating PPE and the theory that selective 5-HT2B antagonists might be effective prophylactic therapies for migraine.

• Authors: K W Johnson, D L Nelson, D K Dieckman, D B Wainscott, V L Lucaites, J E Audia, W M Owton, L A Phebus
• Journal: Cephalalgia : an international journal of headache (Cephalalgia) Vol. 23 Issue 2 Pg. 117-23 (Mar 2003) ISSN: 0333-1024 [Print] England
• PMID: 12603368 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Blood Proteins
• Piperazines
• Receptor, Serotonin, 5-HT2B
• Receptors, Serotonin
• Nitric Oxide
• 1-(3-chlorophenyl)piperazine

Topics

• Animals
• Blood Proteins (metabolism)
• Brain (drug effects, metabolism)
• Dose-Response Relationship, Drug
• Dura Mater (cytology, drug effects, metabolism)
• Electric Stimulation
• Guinea Pigs
• Injections, Intravenous
• Male
• Migraine Disorders (chemically induced, metabolism)
• Nitric Oxide (metabolism)
• Piperazines (administration & dosage)
• Receptor, Serotonin, 5-HT2B
• Receptors, Serotonin (metabolism)
• Reference Values