Home Ingredients Afobazole (Fabomotizole)
Stress & AnxietyMood & Mental Health

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. No sedation, no muscle relaxation, no dependence. Not FDA-approved.

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

Benefits

GAD + adjustment disorders vs diazepam (Phase III pivotal)

In a pivotal multicenter RCT versus diazepam, afobazole was non-inferior to diazepam in generalized anxiety and adjustment disorders, with a superior safety profile: 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, Trial 2

Cardiovascular anxiety

In a real-world cardiovascular comorbid anxiety study, about 70% of patients responded at 30-60 mg/day. A particularly relevant population — benzodiazepines may complicate cardiac care, and afobazole's lack of sedation and 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

Sigma-1-mediated neuroprotection: increases glial cell survival and prevents nitrosative stress in ischemic stroke models. A mechanistic 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 the recommended dosage of Afobazole?

The clinically studied dose is 30 mg/day (10 mg three times daily); cardiovascular anxiety 30-60 mg/day. 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: 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. 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: Generally compatible with most medications. 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 'GAD + adjustment disorders vs diazepam (Phase III pivotal)' and 'Activating profile without sedation'.
  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'.