Antiparkinsonian effects of BAM-1110, a novel ergoline derivative, in MPTP-treated cynomolgus monkeys.
BAM-1110 [(5R,8R,10R)-6-methyl-8-(1,2,4-triazol-l-ylmethyl) ergoline maleate] is a newly synthesized dopamine agonist that produces little anorexic side effects (nausea and vomiting). The current study examines the effects of BAM-1110 on parkinsonian symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, an animal model of Parkinson's disease. First, a significant antiparkinsonian effect of apomorphine hydrochloride (0.3 mg/kg given subcutaneously) was confirmed in these animals. BAM-1110 (0.1, 0.3, and 1 mg/kg subcutaneously) relieved parkinsonian symptoms in a dose-dependent manner. Significant effects were observed at doses of 0.3 and 1 mg/kg and lasted for at least 3 h. BAM-1110, at a dose of 0.3 mg/kg that produced the submaximal antiparkinsonian effect, did not induce significant abnormal behaviors such as hyperactivity and stereotyped behaviors. Significant stereotyped behaviors were observed at 1 mg/kg of BAM-1110. Apomorphine induced hyperactive and stereotyped behaviors in parallel with its antiparkinsonian effect. BAM-1110 appears to be a potentially useful dopamine agonist to treat Parkinson's disease because of its relatively weak drug-induced hyperactive disturbances and anorexic side effects.
Kuno
S
S
Department of Neurology, Utano National Hospital, Kyoto, Japan.
Mizuta
E
E
Sakamoto
H
H
Ichihara
K
K
Nagasaka
M
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001058:Apomorphine / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D015259:Dopamine Agents; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000627:therapeutic use*; D008252:Macaca fascicularis; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D013239:Stereotyped Behavior / Q000187:drug effects; D014230:Triazoles / Q000627:therapeutic use*
C112758:(5R,8R,10R)-6-methyl-8-(1,2,4-triazol-1-ylmethyl)ergoline; D000978:Antiparkinson Agents; D015259:Dopamine Agents; D018491:Dopamine Agonists; D004873:Ergolines; D014230:Triazoles; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine