title: Antinociceptive properties of neurosteroids I. Spinally-mediated antinociceptive effects of water-soluble aminosteroids.
abstract: Four water-soluble aminosteroid intravenous anaesthetic agents (ORG 20380, 20549, 21047 and 20599) were investigated for antinociceptive properties following intrathecal injection in rats. Two compounds, ORG 20380 and 20549, produced spinally-mediated antinociception assessed by tail flick and electrical current nociceptive tests. These effects were dose-related and suppressed by concurrent administration of the GABA(A) receptor antagonist, bicuculline. ORG 21047 and 20599 caused no antinociceptive effects when given intrathecally. Experiments in which nociceptive thresholds were measured after intravenous injections of ORG 20549 showed that subanaesthetic doses of this compound caused antinociceptive effects revealed by both nociceptive tests. This was equal in magnitude to that obtained with intrathecal administration of the same drug. We conclude that ORG 20380 and 20549 produce spinally-mediated antinociception by combination with spinal cord GABA(A) receptors. These spinal receptors are different from the GABA(A) receptors responsible for the anaesthetic effects of these drugs.
authors.affiliation: Department of Anaesthesia, Monash University, Level 5, Block E, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia Department of Anaesthesia, University of Leeds, Leeds, UK.
authors.forename: C S
authors.initials: CS
authors.lastname: Goodchild
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.forename: R
authors.initials: R
authors.lastname: Nadeson
mesh_terms: D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013116:Spinal Cord / Q000502:physiology*; D013256:Steroids / Q000008:administration & dosage / Q000494:pharmacology*; D014867:Water
chemical_list: D018686:Anesthetics, Intravenous; D018756:GABA Antagonists; D013256:Steroids; D014867:Water; D001640:Bicuculline