Clonazepam
Brand name:- Lonazepam , Clonapax , Rivotril 0.5, 1.0, 2.0 mg tab.
Clonazepam is a benzodiazepine. It works by increasing the action of a chemical messenger (GABA) which suppresses the abnormal and excessive activity of the nerve cells in the brain.
Pharmacodynamic:-
The pharmacodynamic properties of clonazepam are common among benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects . 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 Label . Moreover, the agent can also decrease the frequency, amplitude, duration, and spread of discharge in minor motor seizures Label .
Generalized EEG abnormalities are more readily suppressed by clonazepam than are focal EEG abnormalities such as focal spikes . Clonazepam has beneficial effects in generalized and focal epilepsies .
Pharmacokinetics:-
Oral absorption of clonazepam is good. It is 85% bound to plasma proteins, completely metabolized in liver and excreted in urine ; t½ average 24 hours . It does not produce any active metabolite.
Mechanism of action:-
Clonazepam is a highly potent long-acting benzodiazepine. Clonazepam exerts pharmacological effects by acting as a positive allosteric modulator of GABA-A receptors. The GABA-A receptor is a ligand-gated chloride ion selective channel whose endogenous ligand is GABA (gamma-aminobutyric acid). Benzodiazepines facilitate GABA-A action by increasing the frequency of chloride channel opening resulting in hyperpolarization of the neurons and reduced firing, thus producing calming effects on the brain by decreasing the excitability of neurons. In the absence of GABA, benzodiazepines have no effects on GABA-A receptor function.
GABA is an inhibitory neurotransmitter in abundance in the cortex and limbic system. There are three GABA receptors; A, B, and C. However, BZDs act only on GABA-A receptors. Each receptor complex has 2 GABA-binding sites and 1 BZD-binding site and is comprised of five subunits: two alpha, two beta, and one gamma. BZDs do not bind to the same receptor site on the receptor complex as the endogenous ligand GABA but bind to distinct BZD-binding sites situated at the interface between the alpha and gamma subunits. The binding results in a conformational change in the GABA-A receptor's chloride channel that results in the hyperpolarization of the cell and accounts for GABA's inhibitory effect throughout the central nervous system.
GABA receptors are also classified into various BZD receptors based on the isoforms of the alpha subunit. The benzodiazepine type-1 receptors (BZ1), which contain alpha-1 subunits, are abundant in the cortex, thalamus, and cerebellum and are responsible for their anticonvulsant and sedative effects. Whereas benzodiazepine type-2 receptors containing alpha-2 subunits, mostly concentrated in the limbic system, motor neurons, and dorsal horn of the spinal cord, mediate the anxiolytic effects of BZDs.
Used:-
Used in the treatment of anxiety disorder and epilepsy/seizures.
Side effects:-
Depression, Dizziness, Drowsiness, Fatigue, Memory impairment, Blurred vision, Constipation, Sleepiness, Abnormal behavior, Cognitive impairment, Abnormality of voluntary movements, Nervousness, Upper respiratory tract infection, Allergic reaction, Influenza, Pain during periods, Difficulty in speaking, Emotional lability, Decreased libido.
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