TY - JOUR T1 - THE EFFECT OF DISULFIRAM ON THE ACTION AND METABOLISM OF PARALDEHYDE JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 19 LP - 25 VL - 119 IS - 1 AU - M. L. Keplinger AU - J. A. Wells Y1 - 1957/01/01 UR - http://jpet.aspetjournals.org/content/119/1/19.abstract N2 - The evidence presented here indicates that interference with the metabolism of acetaldehyde results in a delay in the disappearance of paraldehyde from the circulation with a commensurate prolongation of the hypnotic effect of this substance. The fact that acetaldehyde levels remain elevated in association with the sustained high levels of paraldehyde indicates that the primary effect of disulfiram is to retard the breakdown of acetaldehyde and suggests that an equilibrium exists in the body between paraldehyde and acetaldehyde. In this way, the rate of removal of paraldehyde and, thus, the persistence of its effect, would be related to the existing level of acetaldehyde and, in turn, to its rate of metabolism. The present situation is in contrast to that associated with the administration of ethyl alcohol following disulfiram. In this latter case, the substantial accumulation of acetaldehyde does not appear to alter the rate of disappearance of alcohol from the circulation (Jacobsen, 1952) and does not enhance or increase the persistence of the symptoms ascribable to alcohol itself. While the manufacturers of disulfiram caution against its use in conjunction with paraldehyde, the authors are unaware of any evidence of an enhanced toxicity due to such a combination. From the present studies it might be anticipated that the effect of such a combination would be, predominantly, an exaggeration of the duration of the hypnotic effect of paraldehyde. ER -