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 late 1990s; clinical registration granted 2006. Manufactured by Pharmstandard (Russia); over-the-counter status. Unique pharmacology: Sigma-1 receptor chaperone agonist as primary mechanism — distinct from all benzodiazepines (direct GABA-A modulators). Sigma-1 chaperone activity enhances GABA-A function indirectly and prevents stress-induced reductions in benzodiazepine site binding. Phase III multicenter RCT (n=150) — afobazole NON-INFERIOR to diazepam in GAD/adjustment disorders, with SUPERIOR safety profile. No sedation, no muscle relaxation, no dependence. Not FDA-approved.

Studied Dose RUSSIAN PHASE III: 30 mg/day (10 mg × 3) × 30 days. CV ANXIETY: 30-60 mg/day × 6 weeks. Standard: 10 mg three times daily × 2-4 weeks. Onset 5-7 days for full effect — not for acute panic. OTC in Russia. No dependence. Not FDA-approved.
Active Compound Fabomotizole / afobazole (5-ethoxy-2-[2-(morpholino)-ethylthio]-benzimidazole hydrochloride) — 2-mercaptobenzimidazole derivative

Benefits

GAD + adjustment disorders vs diazepam (Phase III PIVOTAL)

Syunyakov 2016 — pivotal Phase III multicenter RCT (n=150) vs diazepam. Afobazole NON-INFERIOR to diazepam in GAD and adjustment disorders, with SUPERIOR safety profile. No sedation, no muscle relaxation, no dependence — distinguishing from benzodiazepines. Activating anxiolytic profile preserves cognitive and motor function during daytime treatment. Most rigorous Russian anxiolytic trial in available literature.

Supported by Trial 1

Cardiovascular anxiety

Grigorian 2008 — real-world cardiovascular comorbid anxiety study. 70% responders at 30-60 mg/day × 6 weeks. Particularly relevant population — benzodiazepines may complicate cardiac care, and afobazole's lack of sedation/cognitive impairment is clinically advantageous in patients managing cardiovascular conditions.

Supported by Trial 3

Activating profile without sedation

Distinguishing clinical profile vs benzodiazepines: NO sedation, NO muscle relaxation, NO cognitive impairment, NO dependence, NO withdrawal. Designed via the pharmacogenetic concept of 'anxioselectivity' — anxiolytic activity without benzodiazepine drawbacks. Suitable for daytime treatment preserving cognitive and motor function.

Supported by Trial 2, Trial 1

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.

Supported by Trial 1

Neuroprotective effects

Katnik 2016 — Sigma-1-mediated neuroprotection. Increases glial cell survival; prevents nitrosative stress in ischemic stroke models. Mechanism complement beyond pure anxiolysis — relevant to broader CNS protection contexts.

Supported by Trial 3

Reversible MAO-A inhibition

Reversible monoamine oxidase A inhibition contributes to mood-modulating effects. Reversibility minimizes the dietary tyramine concerns associated with irreversible MAOIs.

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 — supports the long-term mood and resilience benefits.

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.

Pivotal Phase III multicenter clinical trial (n=150) vs diazepam in GAD and adjustment disorders. Non-inferior efficacy with superior safety profile. Most rigorous Russian non-benzodiazepine anxiolytic trial in available literature.

2
Afobazole Pilot Clinical Study

Foundational pilot trial.

Clinical population described in trial publication.

Foundational pilot trial. Demonstrated activating anxiolytic profile without sedation. Established the clinical pharmacology that motivated the Phase III development.

3
Afobazole in Cardiovascular Anxiety

Real-world cardiovascular comorbid anxiety study.

Clinical population described in trial publication.

Real-world cardiovascular comorbid anxiety study. 70% responders at 30-60 mg/day × 6 weeks. Particularly relevant population given benzodiazepine cardiac complications.

Side effects and drug interactions

Common Potential side effects

Generally extremely well-tolerated; SUPERIOR safety profile vs diazepam in Phase III RCT.
NO sedation, NO motor impairment, NO cognitive impairment, NO dependence, NO withdrawal — major advantages over benzodiazepines.
Mild headache (rare).
GI upset (occasional).
Allergic reactions: rare.
Pregnancy/lactation: avoid (insufficient data).
Long-term safety: Russian OTC status since 2006 supports favorable profile.

Important Drug interactions

Generally COMPATIBLE with most medications.
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 Afobazole (Fabomotizole)?

Selective non-benzodiazepine anxiolytic developed at the V.V. Zakusov Research Institute of Pharmacology (Moscow, Russia). International nonproprietary name: fabomotizole. Synthesized late 1990s; clinical registration granted 2006. Manufactured by Pharmstandard (Russia); over-the-counter status.