Desipramine potentiates spinal antinociception by 5-hydroxytryptamine, morphine and adenosine.
The effects of pretreatment with desipramine, a selective noradrenaline (NA) uptake blocker, on spinal antinociception by 5-hydroxytryptamine (5-HT), morphine and an adenosine analog (NECA) in the rat hot-plate test were examined to determine if endogenous NA is involved in the spinal action of these agents. Desipramine, 25 mg/kg, had no significant intrinsic effect in the hot-plate test but potentiated spinal antinociception by NA and 5-HT. Potentiation was more prominent at higher doses of NA and 5-HT. Desipramine also enhanced the action of morphine and NECA, but, in these instances, the greatest enhancement occurred at lower doses. These results, in conjunction with others, suggest that 5-HT releases NA from the spinal cord while morphine and NECA interact synergistically with endogenously released NA.
Sawynok
Jana
J
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia B3H 4H7 Canada.
Reid
Allison
A
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
D012701:Serotonin; D019830:Adenosine-5'-(N-ethylcarboxamide); D009020:Morphine; D000241:Adenosine; D003891:Desipramine; D009638:Norepinephrine