PARABEN PRESERVATIVES BUT NOT SUCCINYLCHOLINE ARE CEREBRAL VASODILATORS INVITRO

Since the increase in intracranial pressure produced by succinyl-choline is temporally associated with intravenous administration, we investigated in vitro a possible direct cerebrovascular effect of this nicotinic drug. Isometric responses were recorded from dog and guinea pig basilar artery rings suspended in modified Krebs' solution at 37°C. After precontracting with a voltage (KCl)- or a receptor (5-hydroxytryptamine)-mediated agonist, cumulative concentration-relaxation curves were established for: pure succinyl-choline; Quelicin® from multidose vials containing 20 mg/ml succinylcholine, 1.8 mg/ml methylparaben, and 0.2 mg/ml propylparaben; Anectine® from single-dose vials containing 10 mg/ml succinylcholine; multidose Anectine® containing 20 mg/ml succinylcholine and 1.0 mg/ml methylparaben; and methylparaben and propylparaben alone. When required, the endothelium of dog artery was removed by gentle mechanical rubbing and the response to the drugs reevaluated. Both Quelicin® and multidose Anectine® produced statistically significant (P < 0.05) relaxation; Quelicin® was the more potent of the two. Methylparaben and propylparaben produced relaxation in an additive manner and completely accounted for the relaxation produced by Quelicin® and multidose Anectine®. The vascular relaxation was found to be independent of the presence of a functional endothelium. Consistent with a nicotinic induced contraction, pure succinylcholine maintained vessel tone. It is concluded that the pharmaceutically ubiquitous preservatives methylparaben and propylparaben but not pure succinylcholine have vasoactive properties in vitro.