Action at the mu receptor is sufficient to explain the supraspinal analgesic effect of opiates

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 238; no. 3; pp. 1039 - 1044
• Main Authors: FANG, F. G, FIELDS, H. L, LEE, N. M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.09.1986
• Subjects: Analgesia; Analgesics; Animals; Applied sciences; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Tolerance; Enkephalin, Leucine - analogs & derivatives; Enkephalin, Leucine - pharmacology; Enkephalin, Leucine-2-Alanine; Enkephalin, Methionine - analogs & derivatives; Enkephalin, Methionine - pharmacology; Exact sciences and technology; Male; Medical sciences; Mice; Mice, Inbred ICR; Naloxone - pharmacology; Narcotics - pharmacology; Neuropharmacology; Other techniques and industries; Pharmacology. Drug treatments; Protein Precursors - pharmacology; Receptors, Opioid - drug effects; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Spinal Cord - drug effects; Time Factors; Vertebrata; Mammalia; Analgesic; Pain; Mouse; Animal; Rodentia; Intracerebral administration; Thermal stimulus; Opiates; Cerebral ventricle; Opiate receptor μ
• ISSN: 0022-3565; 1521-0103

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.