Methyl p-hydroxybenzoate (E-218) a preservative for drugs and food is an activator of the ryanodine receptor Ca(2+) release channel

1. Haloperidol is a drug used in the management of several psychotic disorders and its use has been linked to Neuroleptic Malignant Syndrome. In the present study we have investigated the effect of a commercial preparation of haloperidol, Serenase, on skeletal muscle sarcoplasmic reticulum. 2. Addition of Serenase to isolated terminal cisternae caused a rapid release of calcium. We tested whether the active Ca(2+)-releasing substance was haloperidol or another compound present in the preparation. 3. Our results show that methyl p-hydroxybenzoate, one of the preservatives and a commonly used anti-microbial agent (E-218) is an activator of Ca(2+) release (E.C. 50=2.0 mM), mediated by a ruthenium red-sensitive Ca(2+) release channel present in skeletal muscle terminal cisternae.