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.