Homotaurine (also known as tramiprosate (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

), 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 an organic compound that is widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine, and accounts for up to 0.1% of total human body weight. It ...

, 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 GABA. For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic neuron produces GABA. A ...

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 (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 (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 and inhibit the formation of neurotoxic aggregates. Homotaurine has also shown

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

activities, reduction in skeletal muscle tonus, and

hypothermic Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...

activity. Homotaurine has been reported as a GABA antagonist, as well as a GABA agonist. ''

In vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and ...

'' studies have found that homotaurine is a GABA_A partial agonist as well as a GABA_B 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 neuropsychiatric behavioral syndrome that is characterized by abnormal movements, immobility, abnormal behaviors, and withdrawal. The onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during ...

induced by baclofen (the prototypical GABA_B agonist), and was able to produce analgesia via the GABA_B receptor, an effect that was abolished when CGP-35348, a GABA_B 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 of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

of homotaurine, acamprosate.

References

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