RP-67580, a specific tachykinin NK1 receptor antagonist, relieves chronic hyperalgesia in diabetic rats.
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.
Courteix
C
C
Laboratoire de Pharmacologie Médicale, Faculté de Médecine, Clermont-Ferrand, France.
Lavarenne
J
J
Eschalier
A
A
D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000502:physiology
D000700:Analgesics; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P