Methyl p-hydroxybenzoate (E-218) a preservative for drugs and food is an activator of the ryanodine receptor Ca2+release channel

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Abstract
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 Ca2+‐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 Ca2+ release (E.C.50=2.0 mM), mediated by a ruthenium red‐sensitive Ca2+ release channel present in skeletal muscle terminal cisternae. British Journal of Pharmacology (2000) 131, 335–341; doi:10.1038/sj.bjp.0703571