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

1 Haloperidol is a drug used in the management of several psychotic disorde rs and its use has been linked to Neuroleptic Malignant Syndrome. In the pr esent 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 releas e of calcium. We tested whether the active Ca2+-releasing substance was hal operidol 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 Ca2+ re lease (E.C.50 = 2.0 mM), mediated by a ruthenium red-sensitive Ca2+ release channel present in skeletal muscle terminal cisternae.