Experimental study of dimebon kinetics

Tishchenkova, I. F.; Agapitova, I. V.; Dorokhov, V. V.; Bobrov, V. I.

doi:10.1007/bf00778970

Cited by 2 publications

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“…After oral dosing with an immediate release (IR) tablet, latrepirdine is rapidly and extensively metabolized in the liver, primarily by cytochrome P450 2D6 (CYP2D6) and to a lesser extent by CYP2C19, CYP3A4, monoamine oxidases A and B. Available animal and human data suggest substantial firstpass gut and hepatic metabolism following oral administration, resulting in very low oral bioavailability (4).…”

Section: Introductionmentioning

confidence: 99%

Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example

Chew

Mordenti²,

Yeoh

et al. 2016

Pharm Res

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Section: Introductionmentioning

confidence: 99%

Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example

Chew

Mordenti²,

Yeoh

et al. 2016

Pharm Res

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“…Pharmacokinetic studies in animals would suggest that this protracted cognitive effect is unlikely to be due to the sustained presence of the drug. While there are no published data available in primates, the half‐life of dimebolin is ∼1.1 h in the rabbit and ∼2 h in the rat (Tishchenkova et al ., 1991). Thus, the mechanism of this pharmacokinetic–pharmacodynamic discordance is unknown, but we have observed the phenomenon with drugs from other classes (e.g.…”

Section: Discussionmentioning

confidence: 99%

The acute effects of dimebolin, a potential Alzheimer's disease treatment, on working memory in rhesus monkeys

Webster

Wilson

Lee

et al. 2011

British J Pharmacology

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BACKGROUNDDimebolin (latrepirdine), a compound with multiple potential drug targets, is being evaluated in clinical trials for the treatment of Alzheimer's disease (AD) and preliminary results suggest it can slow the disease process. There is also evidence that dimebolin directly improves aspects of cognition. Here we examined the acute effect of dimebolin on components of working memory in non-human primates, young adult (11-17 years old) and aged (20-31 years old) rhesus macaques. EXPERIMENTAL APPROACHThe effects of dimebolin (3.9-118 mg kg -1 ) on working memory, as measured by performance on delayed matching-to-sample (DMTS), were examined in the normal young adult monkeys and aged adult monkeys. All the monkeys studied were proficient in the performance of a computer-assisted DMTS task. In a subsequent experiment in the same subjects, dimebolin was administered 15 min before a cognitively-impairing dose (20 mg kg -1 ) of scopolamine. KEY RESULTSIn both the young adult and aged monkeys, dimebolin significantly increased the DMTS task accuracies. In young adults, the task improvement was associated with long (retention/retrieval) delay trials, and a protracted enhancement was observed for sessions run 24 h post administration of a single dose. Dimebolin did not significantly attenuate the scopolamine-induced impairment. In the aged monkeys, dimebolin significantly improved the reduced task accuracies associated with long delay intervals. CONCLUSIONS AND IMPLICATIONSHere we demonstrated that dimebolin is able to improve components of working memory in monkeys and to induce a protracted response for at least 24 h after administration of a single dose.

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Experimental study of dimebon kinetics

Cited by 2 publications

References 0 publications

Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example

Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example

The acute effects of dimebolin, a potential Alzheimer's disease treatment, on working memory in rhesus monkeys

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