Studies on the effect of systemic PD134308 (CAM 958) in spinal reflex and pain models with special reference to interaction with morphine and intrathecal galanin.
The effect of intravenous (i.v.) PD134308, which is a CCK-B antagonist, morphine and intrathecal (i.t.) galanin (GAL) on the excitability of the spinal nociceptive flexor reflex and in the hot plate test was examined in rats. PD134308 (1 mg/kg, i.v.) caused a weak, naloxone-reversible depression of the flexor reflex and moderate antinociception in the hot plate test. PD134308 significantly potentiated the antinociceptive effect of morphone, as well as its depressive effect on the flexor reflex. PD134308 and i.t. GAL synergistically depressed the flexor reflex, which was reversed by naloxone. Finally, the magnitude and duration of the depression of the flexor reflex by morphine was synergistically increased by coadministering i.v. PD134308 and i.t. GAL. The results demonstrate that a CCK antagonist directed to the central CCK-B receptor potentiates the analgesic effects of opioid and non-opioid drugs at spinal level in the rat, thus supporting the notion that CCK in the CNS may be an endogenous, physiological opioid antagonist.
Wiesenfeld-Hallin
Z
Z
Karolinska Institute, Department of Clinical Physiology, Huddinge University Hospital, Sweden.
Xu
X J
XJ
Hughes
J
J
Horwell
D C
DC
Hökfelt
T
T
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D005260:Female; D019004:Galanin; D007211:Indoles / Q000494:pharmacology*; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000187:drug effects; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects*
D000700:Analgesics; D007211:Indoles; D010455:Peptides; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D009270:Naloxone; D008536:Meglumine; D009020:Morphine; D019004:Galanin