donepezil and Cocaine Abuse studies

Donepezil: An indan and piperidine derivative that acts as a selective and reversible inhibitor of ACETYLCHOLINESTERASE. Donepezil is highly selective for the central nervous system and is used in the management of mild to moderate DEMENTIA in ALZHEIMER DISEASE.
donepezil : A racemate comprising equimolar amounts of (R)- and (S)-donepezil. A centrally acting reversible acetylcholinesterase inhibitor, its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine.
2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxyindan-1-one : A member of the class of indanones that is 5,6-dimethoxyindan-1-one which is substituted at position 2 by an (N-benzylpiperidin-4-yl)methyl group.

Research Excerpts

Excerpt	Relevance	Reference
" Although donepezil is approved for use in patients and selective for inhibiting acetylcholinesterase over BuChE, no studies have reported cocaine bioavailability in human subjects receiving donepezil."	2.82	Cocaine cardiovascular effects and pharmacokinetics after treatment with the acetylcholinesterase inhibitor donepezil. ( DeSouza, C; Grasing, K; Mathur, D; Moody, DE; Newton, TF; Sturgill, M, 2016)
"Treatment with donepezil increased ratings of 'any' and 'good' drug effect produced by low-dose cocaine, without modifying the response to high-dose cocaine."	2.75	Donepezil treatment and the subjective effects of intravenous cocaine in dependent individuals. ( DeSouza, C; Grasing, K; Mathur, D; Newton, TF, 2010)
"Remarkably, acetylcholinesterase (AChE) inhibitors that act on the brain AChE suppressed both cocaine- and morphine-induced conditioned place preference and blocked the induction and persistence of cocaine-evoked hyperlocomotion."	1.32	Acetylcholine enhancement in the nucleus accumbens prevents addictive behaviors of cocaine and morphine. ( Hikida, T; Kitabatake, Y; Nakanishi, S; Pastan, I, 2003)

Research

Studies (5)

Authors

Clinical Trials (2)

Trial Overview

Trial Outcomes

Cocaine Pharmacokinetics

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	3 (60.00)	29.6817
2010's	2 (40.00)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Grasing, K	2
Mathur, D	2
DeSouza, C	2
Newton, TF	2
Moody, DE	1
Sturgill, M	1
Hikida, T	1
Kitabatake, Y	1
Pastan, I	1
Nakanishi, S	1
Winhusen, TM	1
Somoza, EC	1
Harrer, JM	1
Mezinskis, JP	1
Montgomery, MA	1
Goldsmith, RJ	1
Coleman, FS	1
Bloch, DA	1
Leiderman, DB	1
Singal, BM	1
Berger, P	1
Elkashef, A	1
Takamatsu, Y	1
Yamanishi, Y	1
Hagino, Y	1
Yamamoto, H	1
Ikeda, K	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Donepezil Effects on Cocaine Craving and Pharmacokinetics[NCT00467389]	Phase 2	12 participants (Actual)	Interventional	2007-02-28	Completed
[NCT01495195]	Phase 2	12 participants (Actual)	Interventional	2012-02-29	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Area-Under-the-Curve for Plasma Concentration (NCT00467389)
Timeframe: 0 to 8 hours

Cocaine Safety in Subjects Receiving Donepezil

Intervention	ng-hr/ml (Mean)
Placebo Treatment Period	34,503
Donepezil Treatment Period	40,812

Patients evaluated for clinical and laboratory adverse events (NCT00467389)
Timeframe: Two weeks

Cocaine Subjective Effects

Intervention	Participants with an Adverse Event (Number)
Placebo Treatment Period	0
Donepezil Treatment Period	2

Cocaine Induced 'High' by VAS (visual analogue scale, between 3 and 30 minutes after intravenous dosing, in mm). VAS results ranged from 0 (minimum effect) to 100 (maximum effect). (NCT00467389)
Timeframe: 3 to 30 minutes

Article	Year
Cocaine cardiovascular effects and pharmacokinetics after treatment with the acetylcholinesterase inhibitor donepezil. The American journal on addictions, 2016, Volume: 25, Issue:5 Topics: Administration, Oral; Adult; Biological Availability; Cardiovascular System; Cholinesterase Inhibito	2016
Donepezil treatment and the subjective effects of intravenous cocaine in dependent individuals. Drug and alcohol dependence, 2010, Feb-01, Volume: 107, Issue:1 Topics: Behavior, Addictive; Cholinesterase Inhibitors; Cocaine; Cocaine-Related Disorders; Donepezil; Dose-	2010
Donepezil treatment and the subjective effects of intravenous cocaine in dependent individuals. Drug and alcohol dependence, 2010, Feb-01, Volume: 107, Issue:1 Topics: Behavior, Addictive; Cholinesterase Inhibitors; Cocaine; Cocaine-Related Disorders; Donepezil; Dose-	2010
Donepezil treatment and the subjective effects of intravenous cocaine in dependent individuals. Drug and alcohol dependence, 2010, Feb-01, Volume: 107, Issue:1 Topics: Behavior, Addictive; Cholinesterase Inhibitors; Cocaine; Cocaine-Related Disorders; Donepezil; Dose-	2010
Donepezil treatment and the subjective effects of intravenous cocaine in dependent individuals. Drug and alcohol dependence, 2010, Feb-01, Volume: 107, Issue:1 Topics: Behavior, Addictive; Cholinesterase Inhibitors; Cocaine; Cocaine-Related Disorders; Donepezil; Dose-	2010
A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments. Addiction (Abingdon, England), 2005, Volume: 100 Suppl 1 Topics: Adult; Anticonvulsants; Cocaine-Related Disorders; Donepezil; Female; Humans; Indans; Male; Middle A	2005

Article	Year
Acetylcholine enhancement in the nucleus accumbens prevents addictive behaviors of cocaine and morphine. Proceedings of the National Academy of Sciences of the United States of America, 2003, May-13, Volume: 100, Issue:10 Topics: Acetylcholine; Animals; Cholinesterase Inhibitors; Cocaine; Cocaine-Related Disorders; Conditioning,	2003
Differential effects of donepezil on methamphetamine and cocaine dependencies. Annals of the New York Academy of Sciences, 2006, Volume: 1074 Topics: Amphetamine-Related Disorders; Animals; Behavior, Animal; Cocaine-Related Disorders; Conditioning, P	2006

donepezil and Cocaine Abuse