Clotiazepam
Encyclopedia
Clotiazepam is a thienodiazepine drug which is a benzodiazepine
analog. The clotiazepam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a thiophene
ring. It possesses anxiolytic
, skeletal muscle relaxant, anticonvulsant
, sedative
properties. Stage 2 NREM
sleep is significantly increased by clotiazepam.
. Clotiazepam is also used as a premedicant in minor surgery in France
and Japan
, where the drug is commercially available under the brand names Veratran and Rize, respectively.
, oral tablets
, and sublingual tablets in a cross-over study in six healthy volunteers (median age 28 years) was conducted. The formulations had similar systemic availability. Compared with oral tablets the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly.
, sedative
, hypnotic
, amnesic, anticonvulsant
and muscle relaxant
pharmacological properties. Clotiazepam binds to the benzodiazepine site of the GABAA receptor where it acts as a full agonist; this action results in an enhanced GABA inhibitory effect at the GABAA receptor which results in the pharmacological effects of clotiazepam.
Clotiazepam has a relatively short elimination half-life and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolised via oxidation. Clotiazepam is metabolised to hydroxy-clotiazepam and desmethyl-clotiazepam. After oral ingestion of a single 5 mg dose of clotiazepam by three healthy volunteers the drug was rapidly absorbed. The elimination half-life of the drug and its metabolites range from 6.5 hours to 18 hours. Clotiazepam is 99 percent bound to plasma protein. In elderly men the elimination half-life is longer and in elderly women the volume of distribution is increased. Individuals with liver impairment have a reduced volume of distribution as well as a reduced total clearance of clotiazepam; renal impairment does not effect the kinetics of clotiazepam.
caused by clotiazepam.
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
analog. The clotiazepam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a thiophene
Thiophene
Thiophene is a heterocyclic compound with the formula C4H4S. Consisting of a flat five-membered ring, it is aromatic as indicated by its extensive substitution reactions. Related to thiophene are benzothiophene and dibenzothiophene, containing the thiophene ring fused with one and two benzene...
ring. It possesses anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
, skeletal muscle relaxant, anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
, sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
properties. Stage 2 NREM
NREM
Non-rapid eye movement, or NREM is, collectively, sleep stages 1 – 3, previously known as stages 1 – 4. Rapid eye movement sleep is not included. There are distinct electroencephalographic and other characteristics seen in each stage. Unlike REM sleep, there is usually little or no eye movement...
sleep is significantly increased by clotiazepam.
Indications
Clotiazepam has been trialed and found to be effective in the short-term management of anxietyAnxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
. Clotiazepam is also used as a premedicant in minor surgery in France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
and Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, where the drug is commercially available under the brand names Veratran and Rize, respectively.
Pharmacokinetics
Single dose pharmacokinetics of 5 mg clotiazepam dropsDrop (unit)
The drop is a unit of measure of volume, the amount dispensed as one drop from a dropper. It is often used in giving quantities of liquid drugs to patients, and occasionally in cooking....
, oral tablets
Tablet
A tablet is a pharmaceutical dosage form. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose...
, and sublingual tablets in a cross-over study in six healthy volunteers (median age 28 years) was conducted. The formulations had similar systemic availability. Compared with oral tablets the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly.
Pharmacology
Similar to other benzodiazepines clotiazepam has anxiolyticAnxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
, sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
, hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
, amnesic, anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
and muscle relaxant
Muscle relaxant
A muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics...
pharmacological properties. Clotiazepam binds to the benzodiazepine site of the GABAA receptor where it acts as a full agonist; this action results in an enhanced GABA inhibitory effect at the GABAA receptor which results in the pharmacological effects of clotiazepam.
Clotiazepam has a relatively short elimination half-life and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolised via oxidation. Clotiazepam is metabolised to hydroxy-clotiazepam and desmethyl-clotiazepam. After oral ingestion of a single 5 mg dose of clotiazepam by three healthy volunteers the drug was rapidly absorbed. The elimination half-life of the drug and its metabolites range from 6.5 hours to 18 hours. Clotiazepam is 99 percent bound to plasma protein. In elderly men the elimination half-life is longer and in elderly women the volume of distribution is increased. Individuals with liver impairment have a reduced volume of distribution as well as a reduced total clearance of clotiazepam; renal impairment does not effect the kinetics of clotiazepam.
Side effects
Drowsiness and asthenia are common side effects. There has been a report of hepatitisHepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
caused by clotiazepam.