Trihexyphenidyl potentiation of L-DOPA: reduced effectiveness three years later in MPTP-induced chronic hemiparkinsonian monkeys.
The effects of a combination of trihexyphenidyl and L-DOPA methyl ester given i.m. were studied 3-5 years after MPTP induced hemiparkinsonism in five female adult Macaca nemistrina monkeys. Three years later, these studies were repeated to determine if the drug combination was equally effective. Although the combination of trihexyphenidyl and L-DOPA produced potentiation in both studies, 3 years later it was quantitatively less. This was due primarily to the reduced effectiveness of L-DOPA methyl ester in a dose of 12.5 mg/kg i.m. Even though the combination was less effective in subsequent years, the animals continued to show the same clinical signs of hemiparkinsonism. Reduced effectiveness of the drug combination does not appear to be due to a lessening of MPTP-induced hemiparkinsonism, but rather to the reduced effectiveness of L-DOPA.
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, 48109-0632, USA.
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D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D015259:Dopamine Agents / Q000627:therapeutic use / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007980:Levodopa / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020267:MPTP Poisoning; D008254:Macaca nemestrina; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D016896:Treatment Outcome; D014282:Trihexyphenidyl / Q000627:therapeutic use*
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007980:Levodopa; D014282:Trihexyphenidyl; C035420:levodopa methyl ester