Xaliproden
Encyclopedia
Xaliproden is a drug which acts as a 5HT1A
agonist
. It has neurotrophic and neuroprotective effects in vitro
, and has been proposed for use in the treatment of several neurodegenerative conditions including amyotrophic lateral sclerosis
(ALS) and Alzheimer's disease
.
Development of xaliproden for these two indications was discontinued in 2007 following analysis of Phase III data. While the drug did show an effect on hippocampal
volume (suggesting perhaps a slowing of cell loss), there was insufficient evidence for efficacy in counteracting Alzheimer's related cognitive decline. Similarly while there were some indicators of efficacy in ALS, including a small but clinically noteworthy effect on some functional parameters, the overall benefit did not reach statistical significance
when results across several Phase III trials were averaged. Xaliproden remains under investigation for treatment of chemotherapy-induced peripheral neuropathy.
5-HT1A receptor
The 5-HT1A 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 Gi/Go and mediates inhibitory neurotransmission...
agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
. It has neurotrophic and neuroprotective effects in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
, and has been proposed for use in the treatment of several neurodegenerative conditions including amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
(ALS) and 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...
.
Development of xaliproden for these two indications was discontinued in 2007 following analysis of Phase III data. While the drug did show an effect on hippocampal
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
volume (suggesting perhaps a slowing of cell loss), there was insufficient evidence for efficacy in counteracting Alzheimer's related cognitive decline. Similarly while there were some indicators of efficacy in ALS, including a small but clinically noteworthy effect on some functional parameters, the overall benefit did not reach statistical significance
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
when results across several Phase III trials were averaged. Xaliproden remains under investigation for treatment of chemotherapy-induced peripheral neuropathy.