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Tisolagiline is an investigational, potent and highly selective reversible inhibitor of the enzyme monoamine oxidase B (MAO-B), studied mainly for neurodegenerative and neuropsychiatric conditions. Developed at the Korea Institute of Science and Technology under the code KDS-2010, it has been evaluated in early clinical trials for Alzheimer's disease and related disorders. Unlike older irreversible MAO-B inhibitors, its reversible binding is intended to avoid the compensatory changes that blunt long-term benefit.
- MAO-B inhibition
- Supports dopamine
- Possible neuroprotection (class effect)
Overview
Tisolagiline is an investigational small-molecule drug classified as a reversible inhibitor of monoamine oxidase B (MAO-B) [1]. Chemically it is a phenyl-substituted propanamide carrying a trifluoromethyl group, with the molecular formula C17H17F3N2O and a molar mass of about 322 g/mol. In enzyme assays it is highly potent, with a half-maximal inhibitory concentration near 7.6 nanomolar and roughly 12,500-fold selectivity for MAO-B over the related isozyme MAO-A [1].
The compound was discovered by researchers at the Korea Institute of Science and Technology and is known by the development codes KDS-2010 and SeReMABI [1][2]. It has been advanced toward the clinic by the biotechnology company Neurobiogen, and by the mid-2020s it had passed Phase 1 testing with a reportedly favorable safety profile and moved into Phase 2 evaluation [3]. Because it remains experimental, tisolagiline is not approved for medical use in any country and is available only within research and clinical trial settings.
Research interest centers on conditions marked by reactive astrocytes, the star-shaped support cells of the brain. Preclinical and early clinical work has examined tisolagiline in Alzheimer's disease, Parkinson's disease, and post-traumatic stress disorder, along with other proposed indications such as obesity, amyotrophic lateral sclerosis, and spinal cord injury recovery [1][2][3]. In animal models of Alzheimer's disease, long-term treatment lowered abnormal astrocytic GABA levels, reduced astrogliosis, strengthened synaptic transmission, and rescued learning and memory, outcomes that were not sustained by the older irreversible inhibitor selegiline [1]. Reviews of the monoamine oxidase inhibitor field place reversible, selective MAO-B agents like this one within a broader effort to widen the therapeutic reach of these enzymes beyond their classic use in depression and Parkinson's disease [4].
Mechanism
Monoamine oxidase B is an enzyme anchored to the outer membrane that helps break down amine neurotransmitters and, in reactive astrocytes, drives the aberrant synthesis of the inhibitory neurotransmitter together with hydrogen peroxide [1][2]. Excess astrocytic tonically dampens the activity of neighboring neurons, while hydrogen peroxide promotes further reactivity and neuronal injury, a self-reinforcing cycle implicated in Parkinson's disease, Alzheimer's disease, and related disorders [2]. Tisolagiline binds MAO-B potently and selectively, and crucially it does so reversibly [1].
Irreversible MAO-B inhibitors such as selegiline permanently disable the enzyme, but with prolonged use the brain compensates by increasing an alternative -producing enzyme, diamine oxidase, which restores the aberrant GABA and erodes the benefit [1]. By binding reversibly, tisolagiline suppresses the excess astrocytic without triggering this compensatory pathway, thereby restoring neuronal activity and, in animal studies, improving cognition and motor function over the long term [1][3]. The same reactive- and mechanism has been proposed to underlie its effects in models of post-traumatic stress disorder, where MAO-B inhibition normalized prefrontal GABA and fear-extinction behavior [3].
receptor fingerprint
MAO-BInhibition
Safetyrisks and cautions, not medical advice
There is very little published human safety information, so this is genuinely experimental. The general MAO-B inhibitor cautions apply by default: avoid stacking with serotonergic drugs, and assume selectivity can slip at high exposure. Not an approved medication.
Subjective profileweighing the evidence above
Too early to judge, and honestly so. A reversible MAO-B inhibitor that avoids the compensatory changes blunting the older irreversible drugs is a real idea, but there is almost no published human data behind this one. Rasagiline and selegiline are what actually exist today.
Resources
This entry is here for reference.
Research
- 2019first citedNewly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibit…
- 2025most recentAstrocytic gamma-aminobutyric acid dysregulation as a therapeutic target for posttraumatic stre…
- 1.Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer's disease.
- 2.Revisiting the Role of Astrocytic MAOB in Parkinson's Disease.
- 3.Astrocytic gamma-aminobutyric acid dysregulation as a therapeutic target for posttraumatic stress disorder.
- 4.Monoamine Oxidase Inhibitors: From Classic to New Clinical Approaches.
4 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
What is Tisolagiline used for?
It is an experimental MAO-B inhibitor in the rasagiline and selegiline family, studied for dopamine support; no approved use.
How does Tisolagiline work?
Like its cousins it inhibits MAO-B to slow dopamine breakdown, and the propargylamine class it belongs to is studied for neuroprotection.
Is Tisolagiline well-researched?
No; published human data is very thin, so treat it as experimental.
What are the main side effects?
Largely unknown given the lack of human data; the general MAO-B inhibitor cautions apply by default.
Limitations of the evidence
- As an investigational agent, its side-effect profile in humans is still being defined through clinical trials
- Long-term human safety and tolerability remain under study
Notes and cautions
- Early-phase clinical testing reported a generally favorable safety profile
- Reversible, selective MAO-B inhibitors are designed to avoid the dietary tyramine interaction seen with non-selective or irreversible MAO inhibitors