title: Effect on radiolabelled-monoamine uptake in vitro of plasma taken from healthy volunteers administered the antidepressant sibutramine HCl.
abstract: Sibutramine HCl, a monoamine reuptake inhibitor type of antidepressant, was administered to healthy male volunteers as either a single dose (12.5 or 50 mg) or repeated treatment (5-20 mg once daily or 15 mg twice daily). Plasma, obtained at regular intervals during and after sibutramine HCl or placebo treatment, was assayed in vitro for its ability to inhibit the uptake of [3H]-noradrenaline (NA) by rat cortical synaptosomes, [3H]-5-hydroxytryptamine (5HT) by human platelets and [14C]-dopamine (DA) by rat striatal synaptosomes. After both single and repeated sibutramine HCl administration, the rank order of uptake inhibition was [3H]-NA greater than [3H]-5HT greater than [14C]-DA. The level of monoamine uptake inhibition increased on daily administration to a plateau 4-6 days after initiation of treatment, for example, approximately 60% and 40% inhibition of [3H]-NA and [3H]-5HT, respectively, following 15 mg sibutramine HCl twice daily. The pattern of monoamine uptake inhibition following sibutramine HCl administration to man is similar to that observed in sibutramine HCl-treated rats, and probably at least partly reflects inhibition of uptake by drug metabolites in both species. The inhibition of monoamine uptake following sibutramine HCl administration to man is consistent with an antidepressant effect.
authors.affiliation: Boots Pharmaceuticals Research Department, Nottingham, UK.
authors.forename: G P
authors.initials: GP
authors.lastname: Luscombe
authors.forename: N A
authors.initials: NA
authors.lastname: Slater
authors.forename: M B
authors.initials: MB
authors.lastname: Lyons
authors.forename: R D
authors.initials: RD
authors.lastname: Wynne
authors.forename: M L
authors.initials: ML
authors.lastname: Scheinbaum
authors.forename: W R
authors.initials: WR
authors.lastname: Buckett
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D003503:Cyclobutanes / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010949:Plasma / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D003503:Cyclobutanes; D004298:Dopamine; C058254:sibutramine; D009638:Norepinephrine