Homotaurine
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Homotaurine, also known as tramiprosate ( INN), 3-amino-1-propanesulfonic acid, or 3-APS, is a natural sulfonic acid found in seaweed. It is analogous to
taurine Taurine (), or 2-aminoethanesulfonic acid, is a naturally occurring amino sulfonic acid that is widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine. It is named after Latin (cogna ...
, but with an extra carbon in its chain. It has
GABAergic In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter gamma-aminobutyric acid (GABA). For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic ...
activity, apparently by mimicking GABA, which it resembles. Homotaurine was investigated in a Phase III clinical trial as a potential treatment for
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
(AD) that did not show efficacy. However, post-hoc analyses have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease-modifying effect. A study in cognitive impairment done in 2018 did show positive benefits. Homotaurine is currently in a phase 3 study with expected FDA approval as the first disease modifying drug for AD.


Medical use

Acamprosate Acamprosate, sold under the brand name Campral, is a medication which reduces cravings in alcoholism. It is thought to stabilize neurotransmission, chemical signaling in the brain that would otherwise be disrupted by alcohol withdrawal. When us ...
(''N''-acetyl homotaurine) was approved by the FDA in 2004 to treat
alcohol dependence Alcohol dependence is a previous (DSM-IV and ICD-10) psychiatric diagnosis in which an individual is physically or psychologically dependent upon alcohol (also chemically known as ethanol). In 2013, it was reclassified as alcohol use disorder ...
.


Biochemical properties

In preclinical studies it had been found to bind to soluble
amyloid beta Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor prot ...
and inhibit the formation of neurotoxic aggregates. Homotaurine has also shown
anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...
activities, reduction in skeletal muscle tonus, and hypothermic activity. Homotaurine has been reported as a
GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...
antagonist, as well as a GABA agonist. ''
In vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
'' studies have found that homotaurine is a GABAA partial agonist as well as a GABAB receptor partial agonist with low efficacy, becoming an antagonist and displacing the full agonists GABA and baclofen at this receptor. In a study in rats, homotaurine reversed the
catatonia Catatonia is a complex syndrome most commonly seen in people with underlying mood disorders, such as major depressive disorder, or psychotic disorders, such as schizophrenia. People with catatonia exhibit abnormal movement and behaviors, wh ...
induced by baclofen (the prototypical GABAB agonist), and was able to produce analgesia via the GABAB receptor, an effect that was abolished when CGP-35348, a GABAB receptor antagonist was applied. In a human study homotaurine selectively and fully inhibits the formation of Aβ42 oligomers at the clinical dose, without evidence of vasogenic edema. One study in rats showed that homotaurine suppressed ethanol-stimulated dopamine release, as well as ethanol intake and preference in rats in a way similar to the ''N''-acetyl
derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...
of homotaurine,
acamprosate Acamprosate, sold under the brand name Campral, is a medication which reduces cravings in alcoholism. It is thought to stabilize neurotransmission, chemical signaling in the brain that would otherwise be disrupted by alcohol withdrawal. When us ...
.


References

{{GABAergics Anticonvulsants Sulfonic acids Amines Neuroprotective agents GABAA receptor agonists GABAB receptor antagonists