title: Duration of drug action of dopamine D2 agonists in mice with 6-hydroxydopamine-induced lesions.
abstract: Although 6-hydroxydopamine-induced (6-OHDA-induced) rats are a well-known Parkinson's disease model, the effects of dopamine D2 agonists in mice with 6-OHDA-induced lesions are not completely understood. We produced mice with 6-OHDA-induced lesions and measured their total locomotion counts following administration of several dopamine D2 agonists (pramipexole, ropinirole, cabergoline, rotigotine, apomorphine, talipexole, and quinelorane). Cabergoline showed the longest duration of drug action, which was in agreement with its long-lived anti-Parkinson effects in rats and humans. In contrast, pramipexole and ropinirole had notably short durations of drug action. We demonstrated that mice with 6-OHDA-induced lesions accompanied with significant lesions in the striatum may be reasonable models to predict the action duration of anti-Parkinson drug candidates in humans.
authors.affiliation: Central Research Laboratory, Kissei Pharmaceutical Co. Ltd, Azumino, Nagano, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuchioka
authors.forename: Fumiki
authors.initials: F
authors.lastname: Oana
authors.forename: Takayuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ijiro
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kaidoh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratochi
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000493:pharmacokinetics*; D001058:Apomorphine / Q000493:pharmacokinetics; D001381:Azepines / Q000493:pharmacokinetics; D052160:Benzothiazoles / Q000493:pharmacokinetics; D000077465:Cabergoline; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000493:pharmacokinetics*; D004873:Ergolines / Q000493:pharmacokinetics; D007211:Indoles / Q000493:pharmacokinetics; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000473:pathology / Q000523:psychology; D000077487:Pramipexole; D011804:Quinolines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics; D013876:Thiophenes / Q000493:pharmacokinetics
chemical_list: D000978:Antiparkinson Agents; D001381:Azepines; D052160:Benzothiazoles; D018491:Dopamine Agonists; D004873:Ergolines; D007211:Indoles; D011804:Quinolines; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C046649:ropinirole; C024763:talipexole; D000077487:Pramipexole; C047508:rotigotine; D016627:Oxidopamine; D000077465:Cabergoline; D001058:Apomorphine; C047726:quinelorane