Effect of tachykinin receptor antagonists in experimental neuropathic pain

• Published in: European journal of pharmacology 1998-11, Vol.361 (2), p.175-184
• Main Authors: Coudoré-Civiale, Marie-Ange, Courteix, Christine, Eschalier, Alain, Fialip, Joseph
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Benzamides - pharmacology; Benzamides - therapeutic use; Biological and medical sciences; Biphenyl Compounds - pharmacology; Biphenyl Compounds - therapeutic use; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Denervation; Diabetes Mellitus, Experimental - physiopathology; Indoles - pharmacology; Indoles - therapeutic use; Intrathecal injection; Isoindoles; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurokinin-1 Receptor Antagonists; Neurology; Neuropathic pain; Neuropharmacology; Pain - drug therapy; Pharmacology. Drug treatments; Piperidines - pharmacology; Piperidines - therapeutic use; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-2 - antagonists & inhibitors; Receptors, Neurokinin-3 - antagonists & inhibitors; Receptors, Tachykinin - antagonists & inhibitors; Sciatic Nerve; Tachykinin receptor antagonist
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00722-5

The intrathecal effect of 0.1 to 10 μg of RP-67,580 (3 aR,7 aR)-7,7-diphenyl-2[1-imino-2(2-methoxyphenyl)-ethyl]perhydroisoindol-4-onehydro chloride, CP-96,345 (2S,3S)- cis-(2(diphenylmethyl)- N-[(2-methoxyphenyl) methyl]-1-azabicyclo[2.2.2]octan-3-amine), SR-140,333 ( S)-(1-{2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl}-4-phenyl-1-azonia-bicyclo[2.2.2.]octane,chloride), all neurokinin (NK) 1-receptor antagonists, SR-48,968 ( S)- N-methyl- N[4-(4-acetylamino-4-[phenylpiperidino)-2-(3,4-dichlorophenyl)-butyl]benzamide, a tachykinin NK 2 receptor antagonist and SR-142,801 ( S)-( N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl)- N-methyl acetamide, a tachykinin NK 3 receptor antagonist, and of their respective inactive enantiomers on thresholds of vocalization due to a mechanical stimulus in mononeuropathic (sciatic nerve ligature) and diabetic rats, was examined. The tachykinin NK 1 and the NK 2 receptor antagonists were antinociceptive in both models, with a higher effect of the former in diabetic rats. The tachykinin NK 3 receptor antagonist was weakly effective in diabetic rats only. This indicates a differential involvement of the tachykinins according to the model of neuropathic pain, suggesting a potential role for tachykinin receptor antagonists in the treatment of neuropathic pain.