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  • Title: Antinociceptive properties of neurosteroids III: experiments with alphadolone given intravenously, intraperitoneally, and intragastrically.
    Author: Nadeson R, Goodchild CS.
    Journal: Br J Anaesth; 2001 May; 86(5):704-8. PubMed ID: 11575348.
    Abstract:
    The veterinary neurosteroid anaesthetic Saffan has the same formulation as Althesin now withdrawn from human use and is a mixture of two neurosteroids, alphadolone, and alphaxalone. The molecular structures of these two pregnanes and their properties as i.v. anaesthetics were reported to be similar. Preliminary experiments showed that alphadolone caused powerful antinociceptive effects without sedation when given i.p. In this study, alphadolone was given to rats (weight 100-200 g) i.v., i.p., and intragastrically. I.v. injections of alphadolone (25 mg kg(-1)) caused anaesthesia and sedation, whereas i.p. (0.1-100 mg kg(-1)) and intragastric administration (750 mg kg(-1)) produced no such effects. Intragastric alphadolone caused antinociceptive effects assessed with the electrical current threshold test (response 2.2 x pre-drug control values) without sedation. These effects were reversed at the level of the spinal cord by intrathecally-administered bicuculline (10 pmol). We conclude that a metabolite of alphadolone acetate produced in the liver leads to antinociceptive effects after i.p. and intragastric administration of the parent compound. This antinociception involves spinal cord GABA(A) receptors, even though the drug was administered via a non-spinal route.
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