Differential cross-tolerance between analgesia produced by alpha 2-adrenoceptor agonists and receptor subtype selective opioid treatments.
Analgesic cross-tolerance between alpha 2-adrenoceptor and opioid receptor agonists was studied using the mouse tail-flick assay. Mice tolerant to clonidine (0.3 mg/kg s.c.) or xylazine (7 mg/kg s.c.) were cross-tolerant to morphine (5 mg/kg s.c.), nalorphine (70 mg/kg s.c.) and supraspinal [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 4 ng i.c.v.), but not trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl] benzeneacetamide methanesulfonate (U50,488; 5 mg/kg s.c.), spinal DAMGO (10 ng i.t.), supraspinal [D-Pen2,D-Pen5]enkephalin (DPDPE; 9 micrograms i.c.v.) or spinal DPDPE (700 ng i.t.). In the complimentary studies, mice tolerant to morphine and nalorphine were cross-tolerant to both of the alpha 2-adrenoceptor agonists, but U50,488 tolerant mice were not. The results suggest differential interactions between alpha 2-adrenoceptor and mu 1-, mu 2-, delta-, kappa 1- and kappa 3-opioid analgesic circuitry.
Paul
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Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70130.
Tran
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D003000:Clonidine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D004361:Drug Tolerance; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D009269:Nalorphine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D009292:Narcotic Antagonists; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists*; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists; D014991:Xylazine / Q000008:administration & dosage / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D014991:Xylazine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D003000:Clonidine; D009269:Nalorphine