Antiparkinsonian effects of BAM-1110, a novel ergoline derivative, in MPTP-treated cynomolgus monkeys.

Abstract

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.

• Authors: S Kuno, E Mizuta, H Sakamoto, K Ichihara, M Nagasaka
• Journal: Clinical neuropharmacology (Clin Neuropharmacol) 1998 Jan-Feb Vol. 21 Issue 1 Pg. 35-40 ISSN: 0362-5664 [Print] United States
• PMID: 9579283 (Publication Type: Journal Article)

Chemical References

• (5R,8R,10R)-6-methyl-8-(1,2,4-triazol-1-ylmethyl)ergoline
• Antiparkinson Agents
• Dopamine Agents
• Dopamine Agonists
• Ergolines
• Triazoles
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Apomorphine

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Animals
• Antiparkinson Agents (therapeutic use)
• Apomorphine (therapeutic use)
• Behavior, Animal (drug effects)
• Dopamine Agents
• Dopamine Agonists (therapeutic use)
• Dose-Response Relationship, Drug
• Ergolines (therapeutic use)
• Macaca fascicularis
• Male
• Parkinson Disease, Secondary (chemically induced, drug therapy, psychology)
• Stereotyped Behavior (drug effects)
• Triazoles (therapeutic use)