RP-67580, a specific tachykinin NK1 receptor antagonist, relieves chronic hyperalgesia in diabetic rats.

Abstract

The effect of a non-peptide NK1 receptor antagonist, RP-67580, and of its enantiomer, RP-68651, on nociceptive thresholds in normal and streptozocin-induced diabetic rats submitted to paw pressure is reported. RP-67580 (1, 3, 9 mg/kg s.c.) dose dependently reduced the diabetes-induced mechanical hyperalgesia observed 4 weeks after induction of diabetes. In normal rats, RP-67580 failed to increase nociceptive thresholds. RP-68651 was inactive in both diabetic and normal rats. These results suggest that (i) substance P is involved in the diabetes-induced chronic hyperalgesia, and (ii) NK1 receptor antagonists merit to be studied more extensively in relation with this pathological condition.

• Authors: C Courteix, J Lavarenne, A Eschalier
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 241 Issue 2-3 Pg. 267-70 (Sep 14 1993) ISSN: 0014-2999 [Print] Netherlands
• PMID: 7694865 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Indoles
• Isoindoles
• Neurokinin-1 Receptor Antagonists
• 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one
• Substance P

Topics

• Analgesics (pharmacology)
• Analysis of Variance
• Animals
• Diabetic Neuropathies (drug therapy, physiopathology)
• Hyperalgesia (drug therapy, physiopathology)
• Indoles (pharmacology)
• Isoindoles
• Male
• Neurokinin-1 Receptor Antagonists
• Rats
• Rats, Sprague-Dawley
• Stereoisomerism
• Substance P (antagonists & inhibitors, physiology)