Galanin receptor antagonists attenuate spinal antinociceptive effects of DAMGO, tramadol and non-opioid drugs in rats.
The involvement of endogenous galanin to antinociception elicited by intrathecally (i.t.) or systemically administered drugs from different chemical and therapeutic classes was investigated using the rat Randall-Selitto or the rat tail-flick test, in the absence or presence of the i.t. administered galanin receptor antagonists galantide and M-35. Antinociception elicited by i.t. tramadol (24 micrograms), DAMGO (1 microgram), clonidine (48 micrograms), desipramine (6 micrograms) or fenfluramine (60 micrograms) was attenuated by i.t. galantide (2 micrograms); the attenuation reached significance at least at one time point. A partial antagonism by i.t. galantide was also observed against the antinociception of i.p. tramadol (10 mg/kg), i.v. clonidine (1 mg/kg), i.p. desipramine (1 mg/kg), or i.p. dipyrone (1000 mg/kg), but antinociception by i.p. fenfluramine (30 mg/kg) was not affected. Using M-35 (2 micrograms i.t.), the antinociception of i.t. tramadol or DAMGO was attenuated, but no inhibition was observed when clonidine, desipramine or fenfluramine were used i.t. If drugs were administered systemically, only antinociception of i.p. fenfluramine but not that of i.p. tramadol, or i.v. clonidine, or i.p. desipramine or i.p dipyrone was attenuated. In the rat tail flick test, co-injection of either 2 micrograms i.t. galantide or M-35 with i.t. tramadol (12 micrograms) almost abolished the antinociceptive effect, whereas the antinociception of systemically administered tramadol (4.6 mg/kg i.p.) was only partially attenuated by i.t. galantide and not affected by i.t. M-35. Binding studies in dorsal spinal cord tissue showed no affinity of galantide or M-35 to spinal mu-, or delta-, or kappa-opioid receptors and none of the other drugs interfered with the spinal galanin binding site. These data give further support of at least a partial galanin link in spinal processes of antinociception.
Selve
N
N
Abteilung Pharmakologie, Grünenthal GmbH, Aachen, FRG.
Englberger
W
W
Friderichs
E
E
Hennies
H H
HH
Reimann
W
W
Wilffert
B
B
D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects*; D014147:Tramadol / Q000494:pharmacology*
D000700:Analgesics; D000701:Analgesics, Opioid; D004745:Enkephalins; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D014147:Tramadol; D003000:Clonidine