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

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. 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. 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 m M ), mediated by a ruthenium red‐sensitive Ca 2+ release channel present in skeletal muscle terminal cisternae. British Journal of Pharmacology (2000) 131 , 335–341; doi: 10.1038/sj.bjp.0703571