Sigmoidal admission rate-dependence of toluene narcotic potency in rats: comparison with nitrous oxide

Aromatic solvents, such as toluene, can cause depression of the central ner vous system functions in both solvent-exposed workers and abusers. The mech anism by which toluene produces its effects is general ly thought to be si mi tar to that produced by general anaesthetics, including inert gases and alcohols. However, whether lipophilic compounds indirectly influence activi ty by perturbing membrane lipids or bind directly to proteins remains a maj or question. In a recent study, the sigmoidal admission rate-dependence of inert gas anaesthetic potency has been suggested to possibly reflect a dire ct narcotic-protein interaction. Therefore, experiments have been carried o ut using seven input toluene flows of 0.5, 1, 2, 3, 4, 5 and 6 l/min. Our r esults indicate that as the rate of toluene delivery increased, the concent ration of toluene required to produce anaesthetic effects increased. Althou gh this was fitted relatively well with linear regression, this fitted bett er when using a sigmoidal model (r = 0.998 vs. r = 0.971, P < 0.01). In add ition, comparison with previous data on nitrous oxide shows a striking simi larity between plots (r = 0.991) which appears consistent with a similar si te of action for both agents. We suggest that all classes of lipophilic age nts could produce their inhibitory effects at similar 'non-specific' sites of action of finite size and limited occupancy. (C) 1999 Elsevier Science I reland Ltd. All rights reserved.