ABSTRACT
Studies have shown that the steroid anaesthetic alphaxalone positively modulates gamma-aminobutyric acid (GABA) receptors in vitro. It has also been reported that positive modulation of GABA(A) receptors in the rat spinal cord can produce antinociception in vivo. This present study looks at the interaction of an intraperitoneal injection (i.p.) of the steroid anaesthetic combination Saffan (alphaxalone 9 mg/ml, alphadolone acetate 3 mg/ml) with GABA(A) receptors in the spinal cord. Full recovery from anaesthesia induced by Saffan 2 ml/kg i.p., as assessed by the rotarod test, occurred after 28.78 +/- 0.86 min. Residual antinociceptive effects were assessed by application of electrical current at two skin sites (neck and tail) and also tail withdrawal from noxious heat. Residual antinociception was observed at both skin sites assessed by the electrical test but not when assessed by noxious heat. The antinociceptive effects in the tail but not the neck were suppressed by intrathecal administration of GABA(A) antagonists (bicuculline and SR-95531). In a separate group of experiments alphaxalone and alphadolone were given i.p. individually at the same doses that were given when formulated in Saffan. Alphaxalone produced sedative and anaesthetic effects with no antinociception. Alphadolone caused no sedation but it did cause antinociceptive effects equal in magnitude to those produced by Saffan. We conclude that Saffan produces antinociception in rats when given i.p. by an interaction with spinal GABA(A) receptors. Furthermore, this antinociception is due to the alphadolone content of the neurosteroid anaesthetic and not the alphaxalone.
Subject(s)
Alfaxalone Alfadolone Mixture/pharmacology , Anesthetics/pharmacology , Nociceptors/drug effects , Pregnanediones/pharmacology , Receptors, GABA-A/physiology , Spinal Cord/metabolism , Steroids/pharmacology , Alfaxalone Alfadolone Mixture/antagonists & inhibitors , Anesthetics/antagonists & inhibitors , Animals , Bicuculline/pharmacology , GABA Antagonists/pharmacology , GABA-A Receptor Antagonists , Male , Pain Measurement , Pyridazines/pharmacology , Rats , Rats, Wistar , Reference Values , Time FactorsABSTRACT
The effect of a specific opioid antagonist, naloxone, was studied in two comparable groups of patients who received i.v. the dose of an anaesthetic agent required to produce loss of consciousness in 50% of subjects. The first group received naloxone 0.006 mg kg-1 5 min before induction of anaesthesia; the second group received a similar volume of saline solution. Thiopentone, Althesin, diazepam, ketamine and propanidid were studied. The differences in percentage of unconscious patients between the naloxone-treated group and the control group were statistically significant for diazepam, ketamine and propanidid. Naloxone did not modify the induction of anaesthesia with thiopentone or Althesin.
Subject(s)
Anesthesia, Intravenous , Anesthetics/antagonists & inhibitors , Consciousness/drug effects , Naloxone/pharmacology , Adult , Alfaxalone Alfadolone Mixture/antagonists & inhibitors , Diazepam/antagonists & inhibitors , Drug Interactions , Female , Humans , Ketamine/antagonists & inhibitors , Male , Middle Aged , Propanidid/antagonists & inhibitors , Thiopental/antagonists & inhibitorsABSTRACT
delta 9-Tetrahydrocannabinol (2.5-80.0 mg/kg) significantly prolonged the anaesthesia induced by ketamine, pentobarbitone, thiopentone, propanidid, and Alfathesin in a dose-dependent manner. Cannabinol and cannabidiol (both 5.0-80.0 mg/kg) were essentially inactive, except that cannabidiol prolonged pentobarbitone-induced anaesthesia. The interaction of delta 9-tetrahydrocannabinol with the anaesthetic agents was postulated to be due to a centrally mediated action, whereas the effect of cannabidiol on pentobarbitone-induced anaesthesia probably depended on a metabolic interaction. The interaction between the cannabinoids in influencing anaesthesia induced by the above agents was examined, and the interactions were found to be complex.
Subject(s)
Anesthetics/antagonists & inhibitors , Cannabinoids/pharmacology , Alfaxalone Alfadolone Mixture/antagonists & inhibitors , Animals , Dose-Response Relationship, Drug , Dronabinol/pharmacology , Drug Interactions , Female , Ketamine/antagonists & inhibitors , Mice , Pentobarbital/antagonists & inhibitors , Propanidid/antagonists & inhibitors , Thiopental/antagonists & inhibitorsABSTRACT
In rats, the sleeping time induced by overdosage with eight steroid anesthetics--alfathesin, 3-(3-oxo-17beta-hydroxy-19-nor-4-androsten-17alpha-yl)-propionic acid-lactone (SC-8109), 21-hydroxy=5alpha-pregnane-3,20-dione (P-234), 4-pregnene-3,11,20-trione (Bio.66), 17-hydroxy-3-oxo-4-androstene-17alpha-propionic acid-gamma-lactone(SC-5233),3alpha-hydroxy-5beta-pregnane-11,20-dione, 5beta-pregnane-3,11,20-trione (U-1373), and hydroxydione--was abolished or considerably reduced by a variety of catatoxic compounds, particularly 3beta-hydroxy-20-oxo-5-pregnene-16alpha-carbonitrile (PCN), 9alpha-fluoro-11beta,17-dihydroxy-3-oxo-4-androstene-17alpha-propionic acid potassium salt (CS-1), prednisolone, ethylestrenol and spironolactone. Phenobarbital and diphenylhydantoin, two non-steroidal stimulators of hepatic microsomal drug metabolism, were also highly effective. In contrast, triamcinolone, estradiol,progesterone, desoxycorticosterone and hydroxydione, which exert little or no catatoxic activity, failed to significantly diminish anesthesia or sedation.
