title: Effect of ibopamine and the active metabolite epinine on the catecholamine content of rat hypothalamus and brainstem in vitro.
abstract: The effect of ibopamine (IBO) (SB 7505, SK&F 100168-A), a new drug for the treatment of congestive heart failure, and its active metabolite epinine (EPN) (N-methyldopamine), on the catecholamine content of hypothalamus and brainstem was studied in vitro after monoamine oxidase inhibition with pargyline. IBO and EPN increased levels of epinephrine (EPI) in a concentration- and time-dependent manner in both brain areas without significantly affecting the concentration of other catecholamines. Inhibition of either dopamine beta-hydroxylase, the neuronal EPI and norepinephrine uptake system, or esterase hydrolysis of IBO prevented the increase of EPI, whereas inhibition of phenylethanolamine N-methyltransferase, enzymatic dealkylation or the neuronal dopamine or serotonin uptake system had no influence on the increase of EPI levels. These results suggest that IBO after hydrolysis to EPN can be converted enzymatically to EPI by dopamine beta-hydroxylase in hypothalamus and brainstem. EPN seems to be accumulated into adrenergic and noradrenergic neurons by the high affinity uptake system. Changes in the EPI content of the central nervous system neurons might be responsible for some of the pharmacologic effects of IBO.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence.
authors.forename: G K
authors.initials: GK
authors.lastname: Scriba
authors.forename: J A
authors.initials: JA
authors.lastname: Hower
authors.forename: N Y
authors.initials: NY
authors.lastname: Liang
authors.forename: P V
authors.initials: PV
authors.lastname: Fennessey
authors.forename: R T
authors.initials: RT
authors.lastname: Borchardt
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D003846:Deoxyepinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002395:Catecholamines; D015102:3,4-Dihydroxyphenylacetic Acid; C023487:ibopamine; D003846:Deoxyepinephrine; D004298:Dopamine; D009638:Norepinephrine