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Effect of histamine H 2 receptor antagonism on levodopa–induced dyskinesia in the MPTP‐macaque model of Parkinson's disease
Author(s) -
Johnston Tom H.,
van der Meij Anne,
Brotchie Jonathan M.,
Fox Susan H.
Publication year - 2010
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.23069
Subject(s) - dyskinesia , antagonism , mptp , parkinson's disease , levodopa , macaque , medicine , neuroscience , histamine , degenerative disease , pharmacology , central nervous system disease , disease , receptor , psychology
Abstract Levodopa‐induced motor complications, including dyskinesia and wearing off, are troublesome side effects of treatment and impair quality of life in Parkinson's disease (PD) patients. The use of nondopaminergic agents as adjuncts to levodopa are potential options for managing these problems. Here, we asses the ability of the clinically available, selective histamine H 2 antagonist, famotidine (1, 3, and 30 mg/kg) to treat levodopa‐induced dyskinesia and wearing off in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐macaque model of PD. Famotidine (3 mg/kg) increased peak activity, enhanced peak anti‐parkinsonian action (1 and 3 mg/kg), and extended duration of action (3 mg/kg, by 38%) of a low dose of levodopa (compared to low dose levodopa alone). Enhancement of anti‐parkinsonian actions of low dose levodopa by famotidine (3 mg/kg) was associated with only mild, nondisabling dystonia. Famotidine had no effect on the anti‐parkinsonian actions of high dose levodopa (compared to high dose levodopa alone). However, famotidine (1, 3, and 30 mg/kg) had a significant effect on chorea, but not dystonia, induced by high dose levodopa (compared to high dose levodopa alone). Famotidine increased high dose levodopa–induced “good quality” on time, i.e., on time not associated with disabling dyskinesia, by up to 28% (compared to high dose levodopa alone). In conclusion, famotidine, a drug currently available for use in the clinic, can enhance the peak‐dose anti‐parkinsonian actions and extend total duration of action of a low dose of levodopa, without producing disabling dyskinesia. Furthermore, in combination with a higher dose of levodopa, famotidine can reduce peak‐dose levodopa‐induced chorea and improve the quality of on‐time. © 2010 Movement Disorder Society