Interaction between anti-Alzheimer and antipsychotic drugs in modulating extrapyramidal motor disorders in mice.

Abstract

Antipsychotics are often used in conjunction with anti-Alzheimer drugs to treat the behavioral and psychological symptoms of dementia (BPSD). Here, we examined the effects of cholinesterase inhibitors (ChEIs), donepezil and galantamine, on antipsychotic-induced extrapyramidal side effects (EPS) in mice. The effects of serotonergic agents on the EPS drug interaction were also evaluated. Donepezil (0.3-3 mg/kg) did not induce EPS signs by itself; however, it significantly potentiated bradykinesia induction with a low dose of haloperidol (0.5 mg/kg) in dose-dependent and synergistic manners. Galantamine (0.3-3 mg/kg) elicited mild bradykinesia at a high dose and dose-dependently augmented haloperidol-induced bradykinesia. The EPS potentiation by galantamine was blocked by trihexyphenidyl (a muscarinic antagonist), but not by mecamylamine (a nicotinic antagonist). In addition, the bradykinesia potentiation by galantamine was significantly reduced by (±)-8-hydroxy-2-(di-n-propylamino)-tetralin (a 5-HT1A agonist), ritanserin (a 5-HT2 antagonist), and SB-258585 (a 5-HT6 antagonist). The present results give us a caution for the antipsychotics and ChEIs interaction in inducing EPS in the treatment of BPSD. In addition, second generation antipsychotics, which can stimulate 5-HT1A receptors or antagonize 5-HT2 and 5-HT6 receptors, seem to be favorable as an adjunctive therapy for BPSD.

• Authors: Saki Shimizu, Yuto Mizuguchi, Akira Sobue, Mai Fujiwara, Tomoki Morimoto, Yukihiro Ohno
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 127 Issue 4 Pg. 439-45 (Apr 2015) ISSN: 1347-8648 [Electronic] Japan
• PMID: 25850380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Antipsychotic Agents
• Cholinesterase Inhibitors
• Indans
• Nootropic Agents
• Piperidines
• Receptors, Muscarinic
• Serotonin Agents
• Galantamine
• Receptor, Serotonin, 5-HT1A
• Donepezil
• Haloperidol

Topics

• Alzheimer Disease (drug therapy)
• Animals
• Antipsychotic Agents (adverse effects)
• Basal Ganglia Diseases (chemically induced)
• Cholinesterase Inhibitors (adverse effects)
• Donepezil
• Dose-Response Relationship, Drug
• Drug Interactions
• Galantamine (adverse effects)
• Haloperidol (adverse effects)
• Hypokinesia (chemically induced)
• Indans (adverse effects)
• Male
• Mice, Inbred Strains
• Nootropic Agents (adverse effects)
• Piperidines (adverse effects)
• Receptor, Serotonin, 5-HT1A
• Receptors, Muscarinic
• Serotonin Agents (adverse effects)