General
Preferred name
CLONAZEPAM
Synonyms
Ro-54023 ()
RO 5-4023 ()
Rivotril ()
NSC-179913 ()
Ro-5-4023 ()
Clonazepam civ ()
Ravotril ()
Klonopin ()
Klonopin Rapidly Disintegrating ()
Rivatril ()
Clonazepam-d4 (CRM) ()
P&D ID
PD009568
CAS
1622-61-3
106955-87-7
170082-15-2
Tags
available
drug
Approved by
FDA
First approval
1975
Drug Status
illicit
approved
Drug indication
Anticonvulsant
Epilepsy
Seizure disorder
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE
The mean elimination half-life determined for clonazepam is independent of the dose given and has been documented as being about 30-40 hours [F3763, F3796].
PHARMACODYNAMICS
The pharmacodynamic properties of clonazepam are common among benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects [A175423, L5572, F3763, F3787]. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absence seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations, as well as irregular spikes and waves [FDA Label] [A175423, L5572, F3763, F3787]. Moreover, the agent can also decrease the frequency, amplitude, duration, and spread of discharge in minor motor seizures [FDA Label] [F3763]. Generalized EEG abnormalities are more readily suppressed by clonazepam than are focal EEG abnormalities such as focal spikes [L5572]. Clonazepam has beneficial effects in generalized and focal epilepsies [L5572].
MOA
Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body [A175423, A175438, A175441]. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors [A175423, A175438, A175441, F3787]. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons [A175423, A175438, A175441, F3787]. Subsequently, benzodiazepines like clonazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors [A175423, A175438, A175441, F3787, L5572, F3763]. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors [A175423, A175438, A175441, F3787, L5572, F3763]. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells [A175423, A175438, A175441, F3787, L5572, F3763]. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action [A175423, A175438, A175441, F3787, L5572, F3763]. In particular, when out of the ordinary rapid and repetitive electrical signals are released in the CNS, it is proposed that the brain can become over-stimulated and ordinary functions are disrupted - resulting in seizure activity [A175441]. By enhancing the neuro-inhibitory activity of GABA, it is believed that clonazepam can facilitate in decreasing any excessive electrical nerve activity in the CNS that might be contributing to seizures [A175441]. Concurrently, it is also believed that clonazepam's actions in enhancing GABA effects may inhibit neuronal activity proposed to occur in amygdala-centered fear circuits - therefore assisting in the management of anxiety or panic [A175438].
ROE
Approximately 50-70% of a clonazepam dose is excreted in the urine and 10-30% is excreted in the feces as metabolites [F3763, F3796]. The excretion of unchanged clonazepam in the urine is typically less than 2% of the administered dose [F3763, F3796]. Metabolites of clonazepam are present in urine as both free and conjugated (glucuronide and sulfate) compounds [F3763, F3796].
INDICATION
Clonazepam is indicated as monotherapy or as an adjunct in the treatment of Lennox-Gastaut syndrome (petit mal variant), akinetic, and myoclonic seizures [FDA Label] [F3787]. Furthermore, clonazepam may also be of some value in patients with absence spells (petit mal) who have failed to respond to succinimides [FDA Label] [F3787]. Additionally, clonazepam is also indicated for the treatment of panic disorder, with or without agoraphobia, as defined in the DSM-V [FDA Label]. Alternatively, some regional prescribing information note that clonazepam is indicated for all clinical forms of epileptic disease and seizures in adults, especially absence seizures (petit mal) including atypical absence; primary or secondarily generalised tonic-clonic (grand mal), tonic or clonic seizures; partial (focal) seizures with elementary or complex symptomatology; various forms of myoclonic seizures, myoclonus and associated abnormal movements [L5572, F3796]. Such regional label data also has clonazepam indicated for most types of epilepsy in infants and children, especially absences (petit mal), myoclonic seizures and tonic-clonic fits, whether due to primary generalized epilepsy or to secondary generalization of partial epilepsy [F3796].
METABOLISM
Clonazepam is metabolized principally in the liver [F3763, F3796]. The metabolic pathways include hydroxylation, reduction of the nitro groups to amine groups, and the addition of acetate to the amino grouping [F3763, F3796]. In particular, clonazepam is extensively metabolized by reduction to 7-amino-clonazepam and by N-acetylation to 7-acetamido-clonazepam [F3763, F3796]. Hydroxylation at the C-3 position also occurs [F3763, F3796]. Hepatic cytochrome P450 3A4 is implicated in the nitroreduction of clonazepam to pharmacologically inactive metabolites [F3763, F3796].
ABSORPTION
Clonazepam is rapidly and almost entirely absorbed after oral administration as tablets [FDA Label] [F3763, F3796]. Peak plasma concentrations of clonazepam administered by the oral route are reached within 1-4 hours and the associated absorption half-life is about 25 minutes [FDA Label] [F3763, F3796]. The absolute bioavailability is approximately 90% - but with substantially large differences between individuals [FDA Label] [F3763, F3796].
MOA
Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body [A175423, A175438, A175441]. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors [A175423, A175438, A175441, F3787]. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons [A175423, A175438, A175441, F3787]. ; ; Subsequently, benzodiazepines like clonazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors [A175423, A175438, A175441, F3787, L5572, F3763]. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors [A175423, A175438, A175441, F3787, L5572, F3763]. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells [A175423, A175438, A175441, F3787, L5572, F3763]. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action [A175423, A175438, A175441, F3787, L5572, F3763].; ; In particular, when out of the ordinary rapid and repetitive electrical signals are released in the CNS, it is proposed that the brain can become over-stimulated and ordinary functions are disrupted - resulting in seizure activity [A175441]. By enhancing the neuro-inhibitory activity of GABA, it is believed that clonazepam can facilitate in decreasing any excessive electrical nerve activity in the CNS that might be contributing to seizures [A175441]. Concurrently, it is also believed that clonazepam's actions in enhancing GABA effects may inhibit neuronal activity proposed to occur in amygdala-centered fear circuits - therefore assisting in the management of anxiety or panic [A175438].
DESCRIPTION
Clonazepam belongs to the benzodiazepine group of drugs.
(GtoPdb)
PHARMACODYNAMICS
The pharmacodynamic properties of clonazepam are common among benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects [A175423, L5572, F3763, F3787]. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absence seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations, as well as irregular spikes and waves [FDA Label] [A175423, L5572, F3763, F3787]. Moreover, the agent can also decrease the frequency, amplitude, duration, and spread of discharge in minor motor seizures [FDA Label] [F3763].; ; Generalized EEG abnormalities are more readily suppressed by clonazepam than are focal EEG abnormalities such as focal spikes [L5572]. Clonazepam has beneficial effects in generalized and focal epilepsies [L5572].
INDICATION
Clonazepam is indicated as monotherapy or as an adjunct in the treatment of Lennox-Gastaut syndrome (petit mal variant), akinetic, and myoclonic seizures [FDA Label] [F3787]. Furthermore, clonazepam may also be of some value in patients with absence spells (petit mal) who have failed to respond to succinimides [FDA Label] [F3787]. Additionally, clonazepam is also indicated for the treatment of panic disorder, with or without agoraphobia, as defined in the DSM-V [FDA Label].; ; Alternatively, some regional prescribing information note that clonazepam is indicated for all clinical forms of epileptic disease and seizures in adults, especially absence seizures (petit mal) including atypical absence; primary or secondarily generalised tonic-clonic (grand mal), tonic or clonic seizures; partial (focal) seizures with elementary or complex symptomatology; various forms of myoclonic seizures, myoclonus and associated abnormal movements [L5572, F3796]. Such regional label data also has clonazepam indicated for most types of epilepsy in infants and children, especially absences (petit mal), myoclonic seizures and tonic-clonic fits, whether due to primary generalized epilepsy or to secondary generalization of partial epilepsy [F3796].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
19
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Guide to Pharmacology
Ki Database
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
ReFrame library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
39
Molecular Weight
315.04
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
1
Rotatable Bonds
2
Ring Count
3
Aromatic Ring Count
2
cLogP
3.04
TPSA
84.6
Fraction CSP3
0.07
Chiral centers
0.0
Largest ring
7.0
QED
0.68
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Member status
virtual
MOA
GABA(A) BZ Site Receptor Agonists
Therapeutic Class
Anticonvulsants
Source data
