Home Ingredients Afobazole (Fabomotizole)
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Afobazole (Fabomotizole)

Synthetic — 2-mercaptobenzimidazole derivative
Evidence Level
Limited
3 Clinical Trials
6 Documented Benefits
2/5 Evidence Score

Selective non-benzodiazepine anxiolytic developed at the V.V. Zakusov Research Institute of Pharmacology (Moscow, Russia). International nonproprietary name: fabomotizole. Synthesized in the late 1990s; clinical registration granted 2006. Manufactured by Pharmstandard (Russia); over-the-counter status. Unique pharmacology: a Sigma-1 receptor chaperone agonist as the primary mechanism, distinct from benzodiazepines (direct GABA-A modulators). Sigma-1 chaperone activity enhances GABA-A function indirectly and prevents stress-induced reductions in benzodiazepine site binding. Russian trials report little to no sedation, muscle relaxation, or dependence, though these data are largely non-independent. Not FDA-approved.

Studied Dose 30 mg/day (10 mg three times daily); up to 60 mg/day in some Russian studies.
Active Compound Fabomotizole / afobazole (5-ethoxy-2-[2-(morpholino)-ethylthio]-benzimidazole hydrochloride) — 2-mercaptobenzimidazole derivative.

Benefits

Studied for anxiety symptoms in a Russian comparative trial

In a pivotal multicenter RCT versus diazepam, afobazole reduced anxiety-rating scores to a degree the authors reported as comparable to diazepam. This is an unapproved foreign drug evaluated for clinical anxiety disorders, not a dietary-supplement structure/function benefit, and the trial was conducted by researchers associated with the drug's developer: no sedation, no muscle relaxation, and no dependence, distinguishing it from benzodiazepines. The activating anxiolytic profile preserves cognitive and motor function during daytime treatment.

Supported by Trial 1

Anxiety symptoms in Russian patients with cardiac comorbidity (uncited)

In a real-world cardiovascular comorbid anxiety study, a majority of patients were reported to improve, but the underlying study is not cited here and appears in non-independent Russian sources. This describes a medical use of an unapproved drug in people with a diagnosed condition and is not a supplement benefit or a treatment recommendation.

Supported by Trial 3, Trial 1

Activating profile without sedation

Distinguishing clinical profile vs benzodiazepines: Russian trials reported little to no sedation, muscle relaxation, cognitive impairment, dependence, or withdrawal (data are limited and largely non-independent). Designed via the pharmacogenetic concept of 'anxioselectivity' — anxiolytic activity without benzodiazepine drawbacks. Suitable for daytime treatment preserving cognitive and motor function.

Supported by Trial 1, Trial 2

Sigma-1 receptor mechanism (unique)

Sigma-1 receptor chaperone agonist as primary mechanism. Sigma1R chaperone activity enhances GABA-A receptor function indirectly and prevents stress-induced reductions in benzodiazepine site binding. Mechanism distinct from all benzodiazepines (direct GABA-A modulators) — biochemically novel anxiolytic pathway.

Neuroprotective effects

In laboratory and animal (rodent) models, afobazole engaged sigma-1 receptors and reduced markers of neuronal injury. These are preclinical mechanistic findings only; there is no human evidence that afobazole protects the brain, prevents stroke, or treats any neurological condition.

Supported by Trial 1

Reversible MAO-A inhibition

Reversible monoamine oxidase A inhibition has been described as a secondary mechanism in preclinical studies. Reversibility minimizes the dietary tyramine concerns associated with irreversible MAOIs.

Supported by Trial 1

Mechanism of action

1

Sigma-1 receptor (Sigma1R) chaperone agonism

Primary mechanism — Sigma-1 receptor chaperone agonist. Sigma1R is an endoplasmic reticulum chaperone affecting calcium signaling, receptor trafficking, and ER stress responses. Chaperone activity stabilizes GABA-A receptor function and prevents stress-induced reductions in benzodiazepine site binding.

2

GABA-A receptor enhancement (indirect, via Sigma1R chaperone)

Indirect GABA-A enhancement via the Sigma-1 chaperone mechanism — distinct from benzodiazepines' direct allosteric modulation. Maintains GABA-A function under stress conditions where direct modulation would be redundant.

3

BDNF and NGF release promotion

Brain-derived neurotrophic factor and nerve growth factor release promotion. Neuroplasticity mechanism complementing the anxiolytic effect — has been described in preclinical studies; long-term mood and resilience benefits are not established in people.

4

MT1 melatonin receptor agonism, MT3 antagonism

MT1 receptor agonism with MT3 antagonism — modulates the melatonin receptor system contributing to circadian and sleep effects.

5

Reversible MAO-A inhibition

Reversible monoamine oxidase A inhibition contributes mood-modulating activity. Reversibility minimizes tyramine dietary concerns of irreversible MAOIs.

6

Multi-target neuropsychopharmacology

Multi-target pharmacology integrating Sigma-1, GABA-A, neurotrophin, melatonin, and MAO mechanisms — explains the broad anxiolytic profile without the focused sedation of benzodiazepines.

Clinical trials

1
Afobazole vs Diazepam Phase III

Pivotal Phase III multicenter clinical trial (n=150) vs diazepam in GAD and adjustment disorders.

Clinical population described in trial publication.

A multicenter trial (n=150) compared afobazole with diazepam for anxiety symptoms; the developer-associated authors reported reduced anxiety-rating scores with fewer adverse events. This is an unapproved foreign drug studied for clinical anxiety disorders, not a dietary-supplement benefit. Conducted by researchers associated with the drug's developer (V.V. Zakusov Institute); not independently replicated outside Russia.

2
Afobazole Pilot Clinical Study

Foundational pilot trial.

Clinical population described in trial publication.

An early pilot study is referenced in Russian development literature but is not cited here; details and independent verification are not available.

3
Afobazole in Cardiovascular Anxiety

Real-world cardiovascular comorbid anxiety study.

Clinical population described in trial publication.

Real-world cardiovascular comorbid anxiety study. Reported improvement in a majority of participants; this study is not cited in the references below and its methodology and independence cannot be verified here.

Side effects and drug interactions

Common Potential side effects

Reported as well-tolerated in Russian trials, including fewer adverse events than diazepam in a single developer-associated study; independent long-term safety data are limited.
Russian trials reported little to no sedation, motor or cognitive impairment, dependence, or withdrawal; these findings come from limited, largely non-independent data.
Mild headache (rare).
GI upset (occasional).
Allergic reactions: rare.
Pregnancy/lactation: avoid (insufficient data).
Long-term safety: marketed in Russia since 2006, but it has not undergone Western regulatory review and independent long-term safety data are limited.

Important Drug interactions

Formal drug-interaction data are limited; interactions have not been comprehensively studied in independent Western research.
MAOIs: theoretical interactions via reversible MAO-A inhibition; limited clinical concern given reversibility.
Benzodiazepines: theoretical additive anxiolytic effects (used adjunctively in some Russian protocols).
Antidepressants: generally compatible.
Most medications: well-tolerated combination profile.

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Frequently asked questions about Afobazole (Fabomotizole)

What is afobazole?

Afobazole is an anti-anxiety medication developed and prescribed in Russia, designed to ease anxiety without sedation or dependence. It is not approved as a drug or dietary supplement in the US or most Western countries.

What is afobazole used for?

In Russia it is used for anxiety and stress-related conditions. It is a pharmaceutical drug, not a traditional supplement, and Western clinical evidence and regulatory approval are lacking.

How is afobazole used?

In Russian practice it is taken orally at prescribed doses. Because it is an unapproved medication outside Russia, it should not be treated as a casual supplement.

Is afobazole safe?

Russian data suggests good tolerability, but it has not undergone the Western approval process, and independent long-term safety data is limited. As an unapproved drug, it should only be considered under qualified medical supervision.

What is the recommended dosage of Afobazole?

The clinically studied dose is 30 mg/day (10 mg three times daily); up to 60 mg/day in some Russian studies. Always follow the product label and check with a healthcare provider for personal advice.

Is Afobazole safe, and does it have side effects?

For most healthy adults, Afobazole is well tolerated at studied doses. Reported effects can include: Reported as well-tolerated in Russian trials, including fewer adverse events than diazepam in a single developer-associated study; independent long-term safety data are limited. It may also interact with some medications. Afobazole is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Afobazole interact with any medications?

Possible interactions include: Formal drug-interaction data are limited; interactions have not been comprehensively studied in independent Western research. MAOIs: theoretical interactions via reversible MAO-A inhibition; limited clinical concern given reversibility. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Afobazole?

NutraSmarts rates the evidence for Afobazole as Limited (2 out of 5). It is backed by 3 clinical trials and 3 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(3 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Syunyakov TS, Neznamov GG Evaluation of the therapeutic efficacy and safety of the selective anxiolytic afobazole in generalized anxiety disorder and adjustment disorders: Results of a multicenter randomized comparative study of diazepam Ter Arkh. 2016;88(8):73-86. doi:10.17116/terarkh201688873-86.PubMedUsed to support: Phase III multicenter RCT (n=150): afobazole 30 mg/day vs. diazepam 30 mg/day for 30 days in GAD and adjustment disorders; afobazole produced significant HAMA reduction comparable or superior to diazepam without withdrawal syndrome (0% vs. 68%) and with markedly fewer adverse events (15 vs. 199). Supports the anxiety-symptom finding and the activating-profile (non-sedating) description.
  2. Seredenin SB, Antipova TA, Voronin MV, Kurchashova SY, Kuimov AN Interaction of afobazole with sigma1-receptors Bull Exp Biol Med. 2009;148(1):42-44. doi:10.1007/s10517-009-0624-x.PubMedUsed to support: Established afobazole as a selective sigma-1 receptor agonist (the primary mechanistic paper); sigma-1 engagement underlies the non-benzodiazepine anxiolytic and neuroprotective effects. Supports 'Sigma-1 receptor mechanism (unique)' and 'Neuroprotective effects'.
  3. Cuevas J, Behensky A, Deng W, Katnik C Afobazole modulates neuronal response to ischemia and acidosis via activation of sigma-1 receptors J Pharmacol Exp Ther. 2011;339(1):152-160. doi:10.1124/jpet.111.182774.PubMedUsed to support: In-vitro/animal study demonstrating afobazole's sigma-1-mediated neuroprotection against ischemic and acidotic neuronal injury; confirms neuroprotective mechanism. Supports 'Sigma-1 receptor mechanism (unique)' and 'Neuroprotective effects'.