Anaesthesia: the role of adrenergic mechanisms.
The beta-blocker propranolol administered intraperitoneally to rats prior to the barbiturate anaesthetic thiopentone caused a dose-dependent increase in anaesthesia duration. Sotalol, which only poorly crosses the blood-brain barrier, had no such effect, implying a central site of action. The selective beta 1-blockers, metoprolol and atenolol, did not alter thiopentone anaesthesia duration; implying that the effect of propranolol was mediated by a beta 2-receptor. The selective alpha 1-blocker prazocin increased thiopentone anaesthesia duration, while the alpha 1-agonist ST 587 decreased it. Since the alpha 1-agonist methoxamine, which only poorly crosses the blood-brain barrier, was ineffective, a central site of action is indicated. The alpha 2-agonist clonidine markedly increased thiopentone-anaesthesia duration, while the alpha 2-blocker yohimbine, shortened the duration. These effects were shown to be noradrenergic since they were blocked by prior depletion of brain noradrenaline using 6-hydroxydopamine. A model is proposed in which drug-induced alterations in the firing of locus coeruleus cells, or drug-induced changes in the postsynaptic effect of released noradrenaline, may be responsible for modulation of cortical arousal, wakefulness and the processing of sensory stimuli; thus affecting the duration of barbiturate anaesthesia.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001463:Barbiturates; D006892:Hydroxydopamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D009638:Norepinephrine