title: In vitro characterization of cocaine binding sites in human hair.
abstract: In vitro studies were performed to characterize [3H]cocaine binding to dark and light ethnic hair types. In vitro binding to hair was selective, was reversible and increased linearly with increasing hair concentration. Scatchard analyses revealed high-affinity (6-112 nM) and low-affinity (906-4433 nM) binding in hair. Competition studies demonstrated that the potencies of 3beta-(4-bromophenyl)tropane-2beta-carboxylic acid methyl ester, and 5-(4-chlorophenyl)-2,5-dihydro-3H-imidazol[2,1-alpha]isoindole-5-ol and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane were similar to or less than that of (-)-cocaine. The potency of (-)-cocaine was 10-fold greater than that of (+)-cocaine at inhibiting radioligand specific binding to hair. Multivariate analysis indicated that significantly greater nonspecific and specific radioligand binding occurred in dark hair than in light hair. Multivariate analysis also demonstrated a significant ethnicity x sex effect on specific and nonspecific binding to hair. Greater radioligand binding occurred in male Africoid hair than in female Africoid hair and in all Caucasoid hair types. Melanin was considered the most likely binding site for cocaine in hair. Typically, the concentration of melanin is much greater in dark than in light hair. Scatchard analysis indicated that dark hair had a 5- to 43-fold greater binding capacity than light hair. Differences in radioligand binding between hair types appeared to be due to differences in the density of binding sites formed by melanin in hair.
authors.affiliation: Clinical Pharmacology Branch, National Institute on Drug Abuse, NIH, Baltimore, Maryland 21224, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Joseph
authors.forename: W J
authors.initials: WJ
authors.lastname: Tsai
authors.forename: L I
authors.initials: LI
authors.lastname: Tsao
authors.forename: T P
authors.initials: TP
authors.lastname: Su
authors.forename: E J
authors.initials: EJ
authors.lastname: Cone
mesh_terms: D000293:Adolescent; D000328:Adult; D001665:Binding Sites; D001667:Binding, Competitive; D003042:Cocaine / Q000378:metabolism*; D005260:Female; D006197:Hair / Q000378:metabolism*; D006200:Hair Color; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D008543:Melanins / Q000378:metabolism; D008875:Middle Aged; D012965:Sodium Chloride / Q000494:pharmacology; D013696:Temperature
chemical_list: D008543:Melanins; D012965:Sodium Chloride; D003042:Cocaine