title: In vitro melanin binding of NS-49, a phenethylamine class alpha 1A-adrenoceptor agonist.
abstract: Characteristics of the in vitro binding of NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, CAS 137431-04-0) to synthetic melanin were determined and compared with those of other drugs. At all the drug concentrations tested (12.5-200 mumol/l), chloroquine (CAS 54-05-7) had the highest melanin binding (%), followed by ofloxacin (CAS 82419-36-1), NS-49, norephedrine (CAS 154-41-6) and diazepam (CAS 439-14-5). Binding constants (Kb), calculated with the Langmuir adsorption isotherm were, in the order (largest to smallest) chloroquine, ofloxacin, NS-49, norephedrine, the Kb value for NS-49 being one-thirteenth that for chloroquine, one-seventh that for ofloxacin and ten times higher than that for norephedrine. 53% of NS-49 that was bound to synthetic melanin dissociated during 24 h of incubation after the binding experiment. The percent of dissociation for NS-49 was higher than the values for chloroquine (5%) and ofloxacin (39%). After 1 day incubation in the dissociation experiment, the amount of NS-49 bound per mg of melanin was 23 nmol, being less than the amounts of chloroquine (210 nmol) and ofloxacin (78 nmol). These findings indicate that NS-49 has a lower affinity for synthetic melanin than chloroquine and ofloxacin, which have high affinities and therefore accumulate in melanin containing ocular tissues.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan. t.yamada@po.nippon-shinyaku.co.jp
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Okuyama
authors.forename: H
authors.initials: H
authors.lastname: Mukai
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000465:Algorithms; D000813:Anilides / Q000737:chemistry / Q000378:metabolism*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D008543:Melanins / Q000737:chemistry / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: C092989:3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide; D000316:Adrenergic alpha-Agonists; D000813:Anilides; D002021:Buffers; D007202:Indicators and Reagents; D008543:Melanins; D018341:Receptors, Adrenergic, alpha-2