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Action at the mu receptor is sufficient to explain the supraspinal analgesic effect of opiates.
J Pharmacol Exp Ther. 1986 Sep; 238(3):1039-44.JP

Abstract

Mu, delta and kappa opiate receptors have been implicated in the production of analgesia. In order to study the relative contributions of these receptor types to supraspinally mediated analgesia, apparent pA2 values and rank order potencies were determined for i.c.v. injected highly selective opioid agonists in the mouse using a thermal nociceptive test. Drugs used included the prototypical mu agonist morphine, putative mu agonists [D-Ala2, N-methyl-Phe4, Gly5-ol] enkephalin and BAM 22P, putative delta agonists [D-Pen2, D-Pen5] enkephalin, [D-Thr2, Thr6, Leu5] enkephalin and [D-Ser2, Leu5, Thr6] enkephalin and the putative kappa agonists [trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methane sulfonate hydrate] and Dynorphin A (1-13). We were unable to demonstrate significant analgesic potencies for i.c.v. injected Dynorphin A (1-13) or BAM 22P in the absence of marked behavioral abnormalities. The rank order potency of the remaining compounds studied was found to be: [D-Ala2, N-methyl-Phe4, Gly5-ol] enkephalin greater than [D-Thr2, Thr6, Leu5] enkephalin greater than [D-Ser2, Leu5, Thr6] enkephalin greater than Morphine greater than [D-Pen2, D-Pen5] enkephalin greater than [trans-3, 4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methane sulfonate hydrate]. Apparent pA2 values of morphine, [D-Ala2, N-methyl-Phe4, Gly5-ol] enkephalin and [D-Pen2, D-Pen5] enkephalin in naloxone antagonism trials did not differ significantly. These results indicate that although both mu- and delta-selective ligands produce potent analgesia, a single receptor (mu) is sufficient to explain the supraspinal effects of opiate drugs.

Authors

Fang FG
No affiliation info available
Fields HL
No affiliation info available
Lee NM
No affiliation info available

MeSH

AnalgesiaAnimalsDose-Response Relationship, DrugDrug ToleranceEnkephalin, LeucineEnkephalin, Leucine-2-AlanineEnkephalin, MethionineMaleMiceMice, Inbred ICRNaloxoneNarcoticsProtein PrecursorsReceptors, OpioidReceptors, Opioid, deltaReceptors, Opioid, kappaReceptors, Opioid, muSpinal CordTime Factors

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

3018217

Citation

Fang, F G., et al. "Action at the Mu Receptor Is Sufficient to Explain the Supraspinal Analgesic Effect of Opiates." The Journal of Pharmacology and Experimental Therapeutics, vol. 238, no. 3, 1986, pp. 1039-44.
Fang FG, Fields HL, Lee NM. Action at the mu receptor is sufficient to explain the supraspinal analgesic effect of opiates. J Pharmacol Exp Ther. 1986;238(3):1039-44.
Fang, F. G., Fields, H. L., & Lee, N. M. (1986). Action at the mu receptor is sufficient to explain the supraspinal analgesic effect of opiates. The Journal of Pharmacology and Experimental Therapeutics, 238(3), 1039-44.
Fang FG, Fields HL, Lee NM. Action at the Mu Receptor Is Sufficient to Explain the Supraspinal Analgesic Effect of Opiates. J Pharmacol Exp Ther. 1986;238(3):1039-44. PubMed PMID: 3018217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Action at the mu receptor is sufficient to explain the supraspinal analgesic effect of opiates. AU - Fang,F G, AU - Fields,H L, AU - Lee,N M, PY - 1986/9/1/pubmed PY - 1986/9/1/medline PY - 1986/9/1/entrez SP - 1039 EP - 44 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 238 IS - 3 N2 - Mu, delta and kappa opiate receptors have been implicated in the production of analgesia. In order to study the relative contributions of these receptor types to supraspinally mediated analgesia, apparent pA2 values and rank order potencies were determined for i.c.v. injected highly selective opioid agonists in the mouse using a thermal nociceptive test. Drugs used included the prototypical mu agonist morphine, putative mu agonists [D-Ala2, N-methyl-Phe4, Gly5-ol] enkephalin and BAM 22P, putative delta agonists [D-Pen2, D-Pen5] enkephalin, [D-Thr2, Thr6, Leu5] enkephalin and [D-Ser2, Leu5, Thr6] enkephalin and the putative kappa agonists [trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methane sulfonate hydrate] and Dynorphin A (1-13). We were unable to demonstrate significant analgesic potencies for i.c.v. injected Dynorphin A (1-13) or BAM 22P in the absence of marked behavioral abnormalities. The rank order potency of the remaining compounds studied was found to be: [D-Ala2, N-methyl-Phe4, Gly5-ol] enkephalin greater than [D-Thr2, Thr6, Leu5] enkephalin greater than [D-Ser2, Leu5, Thr6] enkephalin greater than Morphine greater than [D-Pen2, D-Pen5] enkephalin greater than [trans-3, 4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methane sulfonate hydrate]. Apparent pA2 values of morphine, [D-Ala2, N-methyl-Phe4, Gly5-ol] enkephalin and [D-Pen2, D-Pen5] enkephalin in naloxone antagonism trials did not differ significantly. These results indicate that although both mu- and delta-selective ligands produce potent analgesia, a single receptor (mu) is sufficient to explain the supraspinal effects of opiate drugs. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/3018217/Action_at_the_mu_receptor_is_sufficient_to_explain_the_supraspinal_analgesic_effect_of_opiates_ DB - PRIME DP - Unbound Medicine ER -