Ethanol, anaesthetics and other lipophilic drugs preferentially inhibit 5-hydroxytryptamine- and acetylcholine-induced noradrenaline release from sympathetic nerves.

The noradrenaline release from the terminal sympathetic nerve fibres was investgated in isolated rabbit hearts perfused with Tyrode solution. Noradrenaline in the perfusate was determined spectrofluorimetrically.--The noradrenaline output evoked by activation of the presynaptic 5-hydroxytryptamine receptors with 5-hydroxytryptamine was decreased by ethanol, diethyl ether, halothane, thiopental and droperidol. There was a good correlation between the negative logarithms of the IC50 values of these compounds and the longarithms of their membrane/buffer partition coefficients (r = 0.993).--Similar to our our previous results with aliphatic alcohols and inhalation anaesthetics, we found that the noradrenaline output induced by activation of the nicotine receptors with acetylcholine was also decreased by barbiturates, propanidid, ketamine, phenytoin and chlorpromazine in a concentration-dependent manner. The inhibitory potency of these compounds on acetylcholine-induced output was also proportional to their hydrophobic property.--Considerably higher concentrations of phenobarbital and ketamine than those which decreased the receptor-mediated noradrenaline output were necessary to inhibit the output evoked by 80 mM K+.--It is concluded that the inhibition of receptor-mediated noradrenaline release by low concentrations of the compounds appears to be due to hydrophobic interaction with membrane constituents of the terminal sympathetic fibres, presumably proteins belonging to the receptor-ionic channel complexes.