title: Pharmacological study of 14 beta-(thioglycolamido)-7,8-dihydro-N(cyclopropylmethyl)-normor phinone (N-CPM-TAMO).
abstract: Opioid effects of 14 beta-(thioglycolamido)-7,8-dihydro-N(cyclopropylmethyl)- normorphinone (N-CPM-TAMO) were studied in the mouse tail-flick and acetic acid writhing assays. In the tail-flick test, N-CPM-TAMO failed to produce any antinociception after i.c.v. administration of up to 300 nmol. However, pretreatment of mice with N-CPM-TAMO produced a time- and dose-dependent antagonism of morphine-induced antinociception. The antagonism by N-CPM-TAMO lasted up to 48 hr, with a maximal effect at 24 hr after i.c.v. administration. Similarly, pretreatment of mice with N-CPM-TAMO at 24 hr also produced a dose-dependent antagonism of kappa-mediated antinociception, induced by U50,488 However, the antagonistic potency of N-CPM-TAMO against U50,488 was 100-fold less than against morphine. Pretreatment with N-CPM-TAMO had no effect on delta opioid receptor-mediated antinociception, as measured with [D-Pen2,D-Pen5]enkephalin. In the writhing assay, N-CPM-TAMO produced a time- and dose-dependent antinociception after i.c.v. administration, with a value of the dose producing 50% analgesia of 18.4 (10.6-31.9) nmol. The antinociceptive effect lasted up to 3 hr after administration. N-CPM-TAMO-induced antinociception was antagonized by coadministration of the kappa-selective antagonist, norbinaltorphimine. Pretreatment of mice with N-CPM-TAMO also produced a time- and dose-dependent antagonism of U50,488-induced antinociception, which lasted up to 72 hr, with a maximal effect at 24 hr after administration. These data indicate that N-CPM-TAMO is a mu-selective, long-term antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University of Rochester, School of Medicine and Dentistry, New York.
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.forename: A
authors.initials: A
authors.lastname: Seyed-Mozaffari
authors.forename: S
authors.initials: S
authors.lastname: Archer
authors.forename: J M
authors.initials: JM
authors.lastname: Bidlack
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004091:Hydromorphone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010147:Pain Measurement; D011759:Pyrrolidines / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*
chemical_list: D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C080253:14-thioglycolamido-7,8-dihydro-N-(cyclopropylmethyl)normorphinone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D004091:Hydromorphone