Brain noradrenaline and anaesthesia: further characterization of the beta-receptor.
The sleeping time induced by thiopentone in rats was markedly prolonged by the (-)-isomer of propranolol while the (+)-isomer was virtually without effect. Since the two isomers are equipotent in their membrane-stabilizing effects but the (-)-isomer is about seven to ten times more potent than the (+)-isomer in beta-blockade this suggests that the potentiation of barbiturate sleeping time is due to blockade of beta-adrenergic receptors. The centrally active beta-agonist, clenbuterol, shortened thiopentone-induced sleeping time in a dose-dependent fashion while the beta-agonist, salbutamol, which fails to cross the blood-brain barrier, was without effect. This suggests a central locus of action. Destruction of the noradrenaline system in the locus coeruleus with 6-hydroxydopamine prevented the effect of a racemic mixture of propranolol in elevating thiopentone-induced sleeping time, thus confirming a noradrenergic mechanism and indicating that the coerulear, rather than the medullary, noradrenaline fibres were involved. Thiopentone-induced sleeping time was potentiated by the selective beta 2 blocker ICI 118551 but not by the selective beta 1 blocker, metoprolol, thus characterizing the relevant beta-receptor type as beta.
D000758:Anesthesia; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine; D010869:Pindolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects; D013874:Thiopental / Q000494:pharmacology; D013997:Time Factors
D001463:Barbiturates; D006892:Hydroxydopamines; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D011433:Propranolol; D010869:Pindolol; D013874:Thiopental; D009638:Norepinephrine