Effect of tachykinin receptor antagonists in experimental neuropathic pain.
The intrathecal effect of 0.1 to 10 microg of RP-67,580 (3aR,7aR)-7,7-diphenyl-2[1-imino-2(2-methoxyphenyl)-ethyl]++ +perhydroisoindol-4-one hydrochloride, 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-dichlorophen yl)-butyl]benzamide, a tachykinin NK2 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 NK3 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 NK1 and the NK2 receptor antagonists were antinociceptive in both models, with a higher effect of the former in diabetic rats. The tachykinin NK3 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.
Coudoré-Civiale
M A
MA
Equipe NPPUA (NeuroPsychoPharmacologie, Université d'Auvergne), Laboratoire de Pharmacologie, Faculté de Pharmacie, Clermont-Ferrand, France. m-ange.coudore@u-clermont1.fr
Courteix
C
C
Eschalier
A
A
Fialip
J
J
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D003714:Denervation; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D054833:Isoindoles; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000188:drug therapy*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D012584:Sciatic Nerve
D000700:Analgesics; D001549:Benzamides; D001713:Biphenyl Compounds; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C073839:SR 48968; C091554:SR 142801; C066892:CP 96345