RP-67580, A SPECIFIC TACHYKININ NK(1) RECEPTOR ANTAGONIST, RELIEVES CHRONIC HYPERALGESIA IN DIABETIC RATS

The effect of a non-peptide NK1 receptor antagonist, RP-67580, and of its inactive enantiomer, RP-68651, on nociceptive thresholds in normal and streptozocin-induced diabetic rats submitted to paw pressure is r eported. RP-67580 (1, 3, 9 mg/kg s.c.) dose dependently reduced the di abetes-induced mechanical hyperalgesia observed 4 weeks after inductio n of diabetes. In normal rats, RP-67580 failed to increase nociceptive thresholds. RP-68651 was inactive in both diabetic and normal rats. T hese 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 cond ition.