Potentiation of morphine and clomipramine analgesia by cholecystokinin -B antagonist CI-988 in diabetic rats.
The aim of this study was to determine the influence of an intrathecally injected cholecystokinin-B (CCK-B) receptor antagonist, CI-988, on the analgesic effect of morphine and clomipramine in diabetic rats. Administered alone, morphine (0.1 mg/kg, i.v.) and clomipramine (3 mg/kg, i.v.) have respectively no effect and only a slight effect on vocalization thresholds to paw pressure in diabetic rats, but, when coadministered with CI-988 (0.1 microg/rat, i.t.), an appreciable antinociceptive effect was observed. This suggests that a spinal blockade of cholecystokininergic system increases the analgesia induced by morphine or clomipramine. A CCK-B receptor antagonist could thus be used to lower dosages of morphine or antidepressant drugs in the management of neuropathic pain in humans, and thereby reduce their side effects.
Coudoré-Civiale
M A
MA
INSERM EPI 9904, Laboratoire de Physiologie, Faculté de Pharmacie, place Henri-Dunant, 63001 Cedex 1, Clermont-Ferrand, France. m-ange.coudore@u-clermont1.fr
Courteix
C
C
Boucher
M
M
Méen
M
M
Fialip
J
J
Eschalier
A
A
Ardid
D
D
D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D000701:Analgesics, Opioid; D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D007211:Indoles; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D008536:Meglumine; D009020:Morphine; D002997:Clomipramine