Clonazepam
5-(2-chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-one
Overview
Clonazepam belongs to Depressants / Benzodiazepines.
Effects
- Sedation, drowsiness, fatigue and reduced anxiety are the core effects. The anticonvulsant and muscle-relaxant actions underlie its therapeutic use.
- Motor and cognitive impairment is common, especially early in treatment: ataxia, impaired coordination and balance, dizziness, slowed reactions and anterograde amnesia.
- Tolerance to the sedative and anticonvulsant effects and physical dependence develop with continued use. Paradoxical reactions (agitation, irritability, disinhibition) occur in a minority of users.
Dosing & duration
Oral tablets and orally disintegrating tablets (0.5, 1 and 2 mg). Oral drops in some countries. Prescription-only. The figures below are medical reference ranges from the drug label, not recreational guidance. Effects are strongly potentiated by alcohol and other CNS depressants, and the drug should never be combined with opioids. Doses are individualised and tapered slowly on discontinuation.
Dose ranges
0.5 mg three times daily
increase by 0.5–1 mg every 3 days, maximum 20 mg/day
0.25 mg twice daily for 3 days, then 0.5 mg twice daily (target ~1 mg/day, label maximum 1–4 mg/day)
Duration
≈20–60 minutes (oral)
Long-acting: clinical effect persists many hours (half-life ≈30–40 h)
Chemical & Physical Properties
| Formula | C15H10ClN3O3 |
| Molar mass | 315.71 g/mol |
| State | Solid |
| Melting point | 237.5 °C |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | pK1 = 1.5, pK2 = 10.5 |
| LogP | 2.41 |
| Solubility | Slightly soluble in water (<100 mg/L at 25 °C), Insoluble in benzene. Slightly soluble in acetone, methanol, chloroform |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 1622-61-3 |
| CAS (enantiomer) | |
| PubChem CID | 2802 |
| InChIKey | DGBIGWXXNGSACT-UHFFFAOYSA-N |
| InChI | InChI=1S/C15H10ClN3O3/c16-12-4-2-1-3-10(12)15-11-7-9(19(21)22)5-6-13(11)18-14(20)8-17-15/h1-7H,8H2,(H,18,20) |
| SMILES | C1C(=O)NC2=C(C=C(C=C2)[N+](=O)[O-])C(=N1)C3=CC=CC=C3Cl |
Synonyms
- Klonopin
- Rivotril
- Clonazepam
Pharmacodynamics & Biochemistry
Clonazepam is a long-acting, high-potency benzodiazepine. It binds the benzodiazepine site of the GABA-A receptor (the α/γ2 subunit interface) and acts as a positive allosteric modulator, increasing the frequency with which the GABA-gated chloride channel opens. The resulting greater chloride influx hyperpolarises the neuron and reduces its firing, producing anticonvulsant, anxiolytic, sedative and muscle-relaxant effects. Its very high receptor affinity, sub-nanomolar Ki at the α1, α2 and α3 GABA-A subunits, together with a long elimination half-life makes clonazepam one of the more potent and slowly cleared benzodiazepines. Beyond its GABAergic action, clonazepam also has serotonergic activity (it influences serotonin synthesis and turnover), which has been proposed to contribute to its usefulness in panic disorder and certain movement disorders.
Biological targets
- GABA-A
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| GABAA receptor α1 subunit | pKi 8.9 | Human |
| GABAA receptor α2 subunit | pKi 8.8 | Human |
| GABAA receptor α3 subunit | pKi 8.7 | Human |
| GABA-A α1β2γ2 receptor | EC50 3.0 nM | Human |
Pharmacokinetics
| Bioavailability | Oral ≈90% |
| Tmax | ≈1–4 h |
| Half-life | ≈30–40 h (reported range ≈19–60 h) |
| Vd | Not reported |
| Protein binding | ≈85% |
| Metabolism | Hepatic CYP3A4 nitro-reduction to 7-aminoclonazepam, followed by acetylation |
| Excretion | Renal (largely as metabolites) |
Toxicology & Safety
Not reported
Long-acting, high-potency benzodiazepine used for epilepsy and panic disorder. Tolerance and physical dependence develop with continued use, and abrupt discontinuation can precipitate a protracted, potentially life-threatening withdrawal syndrome (including seizures), so it must be tapered slowly. The greatest acute danger is additive CNS and respiratory depression when combined with opioids (an FDA boxed warning), alcohol or other sedatives.[3][4]
Legal Status
US: Schedule IV. UK: Class C (Schedule 4 Part I). DE: Anlage III BtMG
Interactions & Contraindications
Drug interactions
Contraindications
No interactions or contraindications listed.
Usage & Context
- Prescription benzodiazepine approved for seizure disorders (including Lennox–Gastaut syndrome and akinetic, myoclonic and absence seizures) and for panic disorder.
- Used off-label for conditions such as acute mania, restless legs syndrome, REM sleep behaviour disorder, tardive dyskinesia and short-term insomnia.
- Also encountered as a drug of misuse. Its potency and long duration make it sought-after and sharply raise overdose risk when combined with opioids or alcohol.
Sources & Evidence
- PubChem: Clonazepam (CID 2802) — identifiers & computed properties
- FDA / DailyMed: Clonazepam prescribing information — pharmacokinetics & metabolism
- Basit H, Kahwaji CI. Clonazepam. StatPearls [Internet] (NCBI Bookshelf, NBK556010) — mechanism, indications, dosing, adverse effects & interactions
- Wikipedia: Clonazepam (pharmacology, pharmacokinetics, adverse effects & legal status) CC BY-SA 4.0
- IUPHAR/BPS Guide to PHARMACOLOGY: clonazepam (ligand 6963) — GABA-A benzodiazepine-site binding data CC BY-SA 4.0
- DEA Diversion Control Division: Controlled Substance Schedules (clonazepam is Schedule IV)
- Anlage III BtMG — Betäubungsmittelgesetz (clonazepam listing incl. exempted low-dose preparations)
- Pritchett DB, Lüddens H, Seeburg PH (1989). Type I and type II GABAA-benzodiazepine receptors produced in transfected cells. Science 245:1389-92.
PMID 2551039 · doi:10.1126/science.2551039
- Norman C, Liin SI, Jauregi-Miguel A, Ottosson NE, Gréen H (2026). In vitro γ-aminobutyric acid A (GABAA) receptor activity and binding interactions at the α+/γ2− interface of 53 prescription and designer benzodiazepines. Commun Chem 9:155.
PMID 41946818 · doi:10.1038/s42004-026-02001-x