Evaluation of the effects of donepezil in psychotic disorders using Swiss albino mice
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20201051Keywords:
Donepezil, Methylphenidate, Haloperidol, Stereotypy, Albino miceAbstract
Background: Schizophrenia as a psychotic disorder is currently treated by various antipsychotic drugs. A large group of patients still remain resistant to the treatment and present in the form of residual cognitive deficits. Donepezil has been advocated at various conferences and seminars for using it in schizophrenia patients. Donepezil is currently approved drug for Alzheimer's disease to improve cognition. Hence, we have tried to assess its role for psychotic models induced by methylphenidate in mice.
Methods: Methylphenidate 5 mg/kg was given by intraperitoneal (i.p) route to induce psychosis in Swiss albino mice (n=6). Donepezil was given alone in a dose of 1 mg/kg and in combination with low dose haloperidol 0.1 mg/kg and groups were compared with haloperidol 0.2 mg/kg. Activity of donepezil was also assessed on the haloperidol induced catalepsy test. Statistical analysis was done with ANOVA followed by Bonferroni’s test.
Results: Methylphenidate successfully induced characteristic stereotypy behaviour in mice similar to amphetamine. Both donepezil 1 mg/kg and haloperidol 0.2 mg/kg showed significant reduction in stereotypy behaviour and there was no statistically significant difference between the two (p<0.05). Effects with donepezil were only slightly inferior to standard while it’s combination (1 mg/kg with haloperidol 0.1 mg/kg) showed comparable results with the standard haloperidol. Donepezil had only marginally enhanced potential to induce catatonia which was statistically insignificant (p>0.05).
Conclusions: Methylphenidate can be used successfully to induce psychosis in animals and donepezil may be a promising and potentially useful drug as add on therapy to routine antipsychotics.
References
Baldessarani RJ, Tarzai FI, Brunton L, Lazo JS, Parker KL. Drug therapy of psychosis and mania. Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 11th ed. New York, NY: McGraw-Hill. 2006: 461-480.
Sadock BJ, Sadock VA. Schizophrenia, Synopsis of psychiatry: Behavioral Sciences or clinical Psychiatry, 10th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 2007: 410-520.
Moller HJ. Bipolar disorder and schizophrenia: distinct illnesses or a continuum. J Clin Psychiatry. 2003;64(6):23-7.
Neill DB, Grant LD, Grossman SP. Selective potentiation oflocomotor effects of amphetamine by midbrain raphe lesions. Physiol Behav. 1972;9(4):655-57.
Solanki RK, Singh P, Munshi D. Current perspectives in the treatment of resistant schizophrenia. Indian J Psychiatry. 2009;51:254-60.
Vogel HG. Inhibition of amphetamine stereotypy in rats. Chapter E.5.3.2. Drug Discovery and Evaluation. Pharmacological assays. 2nd ed. Heidelberg, Germany: Springer; 2002: 535-537.
Westfall TC, Westfall DP, Brunton L, Chabner B, Knollman B. Adrenergic agonists and antagonists. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011: 299.
Kuczenski R, Segal DS. Effects of Methyiphenidate on Extracellular Dopamine, Serotonin, and Norepinephrine: Comparison with Amphetamine. J. Neurochem. 1997;68(5):2032-7.
Morton WA, Stockton GG. Methylphenidate Abuse and Psychiatric Side Effects. Prim Care Companion J Clin Psychiatry. 2000;2(5):159-64.
Balcioglu A, Ren JQ, Carthy MD, Spencer TJ, Biederman J, Bhide PG. Plasma and brain concentrations of oral therapeutic doses of methylphenidate and their impact on brain monoamine content in mice. Neuropharmacology. 2009;57(7-8):687-93.
Nyati P. Psychopharmacogy. In: Pharmacology SEED, 2nd ed. New Delhi: Globalmedik; 2011: 75-79.
Garg PD. In: adult clinical psychiatry, Concise psychiatry for undergraduates. 1 st ed. Sirmor, India: Arya Publishing Company; 2006: 79-80.
Handen BL, Taylor J, Tumuluru R. Psychopharmacological treatment of ADHD symptoms in children with autism spectrum disorder. Int J Adolesc Med Health. 2011;23:167-73.
Yarlagadda A, Clayton AH. Role of cholinergic system and calcium synchronization in schizophrenia. Psychiatry (Edgmont). 2009;6:37-41.
Gabbard GL. In: Treatment of psychiatric disorders by Gabbard, DSM-5th edition. Washington, NY: Amer psychiatric Pub; 2014: 200-204.
Seltzer B. Donepezil: an update. Expert Opin Pharmacother. 2007;8(7):1011-23.