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 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

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 1, 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
Syunyakov 2016 — Afobazole vs Diazepam Phase III (PIVOTAL, PMID 27636931)

Syunyakov 2016 (PMID 27636931) — pivotal Phase III multicenter RCT (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
Neznamov 2001 — Afobazole Pilot Clinical Study (Foundational, PMID 11548440)

Neznamov 2001 (PMID 11548440) — foundational pilot trial. Demonstrated activating anxiolytic profile without sedation. Established the clinical pharmacology that motivated the Phase III development.

3
Grigorian 2008 — Afobazole in Cardiovascular Anxiety (PMID 18379478)

Grigorian 2008 (PMID 18379478) — 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.

More Stress & Anxiety Ingredients

Muscle & Recovery
Magnesium
Magnesium is the fourth most abundant mineral in the body and a cofactor for over 300 enzy…
Cognitive
Ashwagandha
Ashwagandha is an adaptogenic herb that may reduce stress, enhance mood, and support overa…
Cognitive
KSM-66®
KSM-66 Ashwagandha, a standardized root extract, promotes stress relief and cognitive clar…
Cognitive
Phosphatidylserine
Phosphatidylserine (PS) is a phospholipid concentrated in neuronal cell membranes (10-20%…

Explore Other Ingredients

Athletic Performance
Senactiv®
Senactiv® (formerly ActiGin®) is NuLiv Science's patented senolytic sportsceutical — a hig…
Cognitive
L-Theanine
L-Theanine, an amino acid primarily found in green tea (Camellia sinensis), is commonly su…
Cognitive
Suntheanine®
Suntheanine® is a patented, 100% pure L-isomer theanine produced via an enzymatic process…

Frequently asked questions about Afobazole (Fabomotizole)

What is Afobazole (Fabomotizole)?

Selective non-benzodiazepine anxiolytic developed at the V.

What does Afobazole (Fabomotizole) do?

Primary mechanism — Sigma-1 receptor chaperone agonist. Sigma1R is an endoplasmic reticulum chaperone affecting calcium signaling, receptor trafficking, and ER stress responses. In clinical research, Afobazole (Fabomotizole) has been studied for gad + adjustment disorders vs diazepam (phase iii pivotal), cardiovascular anxiety, activating profile without sedation.

Who should take Afobazole (Fabomotizole)?

Afobazole (Fabomotizole) may be most relevant for people interested in stress & anxiety, mood & mental health. It has been clinically studied for gad + adjustment disorders vs diazepam (phase iii pivotal), cardiovascular anxiety, activating profile without sedation. As with any supplement, consult your healthcare provider before starting, especially if you have medical conditions or take prescription medications.

How long does Afobazole (Fabomotizole) take to work?

In clinical trials, effects have been measured at 6 weeks of consistent use. Acute or same-day effects (where applicable) typically appear within hours, but most cumulative benefits — particularly those affecting biomarkers, mood, sleep quality, or chronic symptoms — require 4-12 weeks of regular use to fully assess. If you don't notice benefit after 12 weeks at the appropriate dose, it may not be your responder.

When is the best time to take Afobazole (Fabomotizole)?

For stress and mood goals, Afobazole (Fabomotizole) can be taken in the morning, evening, or split through the day. Effects build gradually over weeks; daily consistency matters more than precise timing. Always check product labeling and follow personalized guidance from your healthcare provider.

Is Afobazole (Fabomotizole) worth taking?

Afobazole (Fabomotizole) has limited clinical evidence (Evidence Level 2/5 on NutraSmarts) — preliminary research suggests potential benefit, but more rigorous trials are needed. Whether it's worth taking depends on your specific goals, what you've already tried, your budget, and your overall supplement strategy. The honest framing: no supplement is essential for most people, and lifestyle factors (sleep, exercise, diet, stress management) typically produce larger effects than any single supplement. Afobazole (Fabomotizole) is most worth trying if its evidence-supported uses align with your specific goals.

What is the recommended dosage of Afobazole (Fabomotizole)?

The clinically studied dose for Afobazole (Fabomotizole) is 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.. Always follow product labeling and consult a healthcare provider for personalized dosing recommendations.

What is Afobazole (Fabomotizole) used for?

Afobazole (Fabomotizole) is studied for gad + adjustment disorders vs diazepam (phase iii pivotal), cardiovascular anxiety, activating profile without sedation. 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.