title: Dantrolene and azumolene inhibit [3H]PN200-110 binding to porcine skeletal muscle dihydropyridine receptors.
abstract: We tested whether the hydantoin muscle relaxants dantrolene, azumolene, or aminodantrolene could alter the binding of [3H]PN200-110 to transverse tubule dihydropyridine receptors or the binding of [3H]ryanodine to junctional sarcoplasmic reticulum Ca2+ release channels. All three drugs inhibited [3H]PN200-110 binding with azumolene (IC50 approximately 20 microM) 3-5 times more potent than dantrolene or aminodantrolene. In contrast, 100 microM azumolene and dantrolene produced a small inhibition of [3H]ryanodine binding (less than 25%) while aminodantrolene was essentially inert. Hence there was a preferential interaction of hydantoins with dihydropyridine receptors instead of ryanodine receptors. Skeletal muscle dihydropyridine receptors may participate in the mechanism of action of dantrolene and azumolene.
authors.affiliation: Department of Physiology, University of Wisconsin Medical School, Madison 53706.
authors.forename: R
authors.initials: R
authors.lastname: el-Hayek
authors.forename: J
authors.initials: J
authors.lastname: Parness
authors.forename: H H
authors.initials: HH
authors.lastname: Valdivia
authors.forename: R
authors.initials: R
authors.lastname: Coronado
authors.forename: K
authors.initials: K
authors.lastname: Hogan
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology*; D004095:Dihydropyridines / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D017275:Isradipine; D008305:Malignant Hyperthermia / Q000378:metabolism; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013552:Swine; D014316:Tritium
chemical_list: D015220:Calcium Channels; D004095:Dihydropyridines; D007093:Imidazoles; D009125:Muscle Relaxants, Central; D010080:Oxazoles; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D019837:Ryanodine Receptor Calcium Release Channel; D014316:Tritium; D012433:Ryanodine; D002110:Caffeine; C061387:azumolene; D003620:Dantrolene; D017275:Isradipine