title: Study of μ- and δ-Opioid Activities in Agents with Various κ-Receptor Selectivity.
abstract: A putative opioid agonist RU-1205 was ineffective within in vitro model of electrically induced contractions of rat ileum assessing the μ- and δ-opioid receptor pathways, while morphine inhibited these contractions in a dose-dependent and naloxone-reversible manners with EC50=2.6×10-7M. In vivo experiments revealed no significant effects of RU-1205 on respiration and gastrointestinal tract contractile activity. In contrast, butorphanol decreased respiration rate by 25% (25-100 mg/kg) and slowed down the transit of labeled particles along the small intestine by 77.1% (1 mg/kg) and by 45.5% (10 mg/kg). Morphine-induced inhibition of peristalsis was dose-dependent with maximum effect (by 68.6%) observed in the dose of 10 mg/kg. It was concluded that the effects of RU-1205 are not related to activation μ- and δ-opioid receptors known to mediate the effects of non-selective opioid agonist morphine and agonist-antagonist butorphanol.
authors.affiliation: Volgograd State Medical University, Volgograd, Russia.
authors.forename: O Yu
authors.initials: OY
authors.lastname: Grechko
authors.affiliation: Volgograd State Medical University, Volgograd, Russia. litvinov.volggmu@mail.ru.
authors.forename: R A
authors.initials: RA
authors.lastname: Litvinov
authors.affiliation: Volgograd State Medical University, Volgograd, Russia.|Volgograd Medical Research Center, Volgograd, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Spasov
authors.affiliation: Volgograd State Medical University, Volgograd, Russia.
authors.forename: A I
authors.initials: AI
authors.lastname: Rashchenko
authors.affiliation: Volgograd State Medical University, Volgograd, Russia.
authors.forename: D M
authors.initials: DM
authors.lastname: Shtareva
authors.affiliation: Research Institute of Physical and Organic Chemistry, Southern Federal University, Rostov-on-Don, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Anisimova
authors.affiliation: Research Institute of Physical and Organic Chemistry, Southern Federal University, Rostov-on-Don, Russia.
authors.forename: V I
authors.initials: VI
authors.lastname: Minkin
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002077:Butorphanol / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005769:Gastrointestinal Motility / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000502:physiology*
chemical_list: C586860:9-(2-morpholinoethyl)-2-(4-fluorophenyl)imidazo(1,2-alpha)benzimidazole; D000701:Analgesics, Opioid; D001562:Benzimidazoles; D009025:Morpholines; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D009020:Morphine; D002077:Butorphanol
keywords: adverse effects; benzimidazole derivatives; δ-opioid receptors; κ-opioid receptor; μ-opioid receptor