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.
Cavagna
D
D
Dipartimento di Medicina Sperimentale e Diagnostica, sezione Patologia Generale, Via Borsari 46, 44100 Ferrara, Italy.
Zorzato
F
F
Babini
E
E
Prestipino
G
G
Treves
S
S
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005520:Food Preservatives / Q000494:pharmacology*; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology; D066298:In Vitro Techniques; D009459:Neuroleptic Malignant Syndrome / Q000209:etiology; D010226:Parabens / Q000494:pharmacology*; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects* / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism
D014150:Antipsychotic Agents; D005520:Food Preservatives; D010226:Parabens; D019837:Ryanodine Receptor Calcium Release Channel; C015358:methylparaben; D006220:Haloperidol; D002118:Calcium