Dimebon
Encyclopedia
Latrepirdine is an antihistamine
drug
which has been used clinically in Russia
since 1983.
Research is continuing in both Russia and western nations into potential applications as a neuroprotective drug to combat Alzheimer's disease
and, possibly, as a nootropic
as well. However, a Phase III clinical trial for Alzheimer's disease (AD) treatment failed to show any benefit. Three other AD trials continue. Dimebon failed in the phase III trial for Huntington disease.
, making it a potential treatment for these and other neurodegenerative diseases. Research suggests that it may also have cognition-enhancing effects in healthy individuals, in the absence of neurodegenerative disease pathology.
Numerous phase III trials for AD were recruiting in 2009.
In July 2009 Pfizer and Medivation announced that latrepirdine will be the proposed international nonproprietary name
for latrepirdine for the treatment of Alzheimer's.
In March 2010 the results of a clinical trial phase III were released. It was announced that the investigational Alzheimer's disease drug dimebon failed in the pivotal CONNECTION trial of patients with mild-to-moderate disease.
.
and NMDA
glutamate receptor
s, and may exert a neuroprotective effect by blocking a novel target that involves mitochondrial pores, which are believed to play a role in the cell death that is associated with neurodegenerative diseases and the aging process. It also blocks a number of other receptors including α-adrenergic, 5-HT2C
, 5-HT5A
, and 5-HT6
. It is of significance to note that latrepirdine lacks any anticholinergic
effects.
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
which has been used clinically in Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
since 1983.
Research is continuing in both Russia and western nations into potential applications as a neuroprotective drug to combat Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
and, possibly, as a nootropic
Nootropic
Nootropics , also referred to as smart drugs, brain steroids, memory enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration...
as well. However, a Phase III clinical trial for Alzheimer's disease (AD) treatment failed to show any benefit. Three other AD trials continue. Dimebon failed in the phase III trial for Huntington disease.
Uses
Latrepirdine is an orally-active small molecule compound that has been shown to inhibit brain cell death in preclinical studies of Alzheimer's disease and Huntington's diseaseHuntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
, making it a potential treatment for these and other neurodegenerative diseases. Research suggests that it may also have cognition-enhancing effects in healthy individuals, in the absence of neurodegenerative disease pathology.
Alzheimer's disease: failed clinical trial
Latrepirdine attracted renewed interest in 2009 after being shown in small preclinical trials to have positive effects on persons suffering from Alzheimer’s disease. Animal studies showing potential beneficial effects on Alzheimer's disease models were shown in Russian research in 2000. Preliminary results from human trials have also been promising. In an initial six-month phase II trial, results have shown that at 12 months there was significant improvement over placebo. Latrepirdine showed promising results in a Phase III equivalent double blind trial in Russia with mild–moderate stage patients. In April 2009, Pfizer and Medivation initiate a phase III trial (CONCERT study) aiming for FDA approval. In March 2010, Pfizer announced that this clinical trial failed to show any benefit for the treatment of Alzheimer's disease patients.Numerous phase III trials for AD were recruiting in 2009.
In July 2009 Pfizer and Medivation announced that latrepirdine will be the proposed international nonproprietary name
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
for latrepirdine for the treatment of Alzheimer's.
In March 2010 the results of a clinical trial phase III were released. It was announced that the investigational Alzheimer's disease drug dimebon failed in the pivotal CONNECTION trial of patients with mild-to-moderate disease.
Huntington's disease
In April 2011 latrepirdine failed in a Phase 3 clinical trial of patients affected with Huntington’s disease. The trial was sponsored by Medivation Inc. and PfizerPfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
.
Pharmacology
Latrepirdine appears to operate through multiple mechanisms of action, both blocking the action of neurotoxic beta-amyloid proteins and inhibiting L-type calcium channels, modulating the action of AMPAAMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
and NMDA
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
glutamate receptor
Glutamate receptor
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...
s, and may exert a neuroprotective effect by blocking a novel target that involves mitochondrial pores, which are believed to play a role in the cell death that is associated with neurodegenerative diseases and the aging process. It also blocks a number of other receptors including α-adrenergic, 5-HT2C
5-HT2C receptor
The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the...
, 5-HT5A
5-HT5A receptor
5-hydroxytryptamine receptor 5A, also known as HTR5A, is a protein which in humans is encoded by the HTR5A gene.- Function :...
, and 5-HT6
5-HT6 receptor
The 5-HT6 receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gs/Go and mediates excitatory neurotransmission. HTR6 denotes the human gene encoding for the receptor.-Distribution:The 5-HT6 receptor is...
. It is of significance to note that latrepirdine lacks any anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
effects.
See also
For Alzheimers disease :- DonepezilDonepezilDonepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate Alzheimer's disease. Common side effects include...
- GalantamineGalantamineGalantamine is used for the treatment of mild to moderate Alzheimer’s disease and various other memory impairments, in particular those of vascular origin...
- Memantine
- RivastigmineRivastigmineRivastigmine is a parasympathomimetic or cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which...
also for Parkinsons