Clinical data | |
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Trade names | Veratran, Rize, Clozan |
AHFS/ Drugs.com | International Drug Names |
Routes of administration | Oral, sublingual, liquid drops |
ATC code | |
Legal status | |
Legal status |
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Pharmacokinetic data | |
Bioavailability | ~90% |
Metabolism | Hepatic |
Elimination half-life | 4 hours [2] |
Excretion | Renal |
Identifiers | |
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CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
ECHA InfoCard | 100.046.920 |
Chemical and physical data | |
Formula | C16H15ClN2OS |
Molar mass | 318.82 g·mol−1 |
3D model ( JSmol) | |
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(what is this?) (verify) |
Clotiazepam [3] (marketed under brand name Clozan, Distensan, Trecalmo, Rize, Rizen and Veratran) is a thienodiazepine drug which is a benzodiazepine analog. The clotiazepam molecule differs from benzodiazepines in that the benzene ring has been replaced by a thiophene ring. [4] It possesses anxiolytic, [5] skeletal muscle relaxant, [6] anticonvulsant, sedative properties. [7] Stage 2 NREM sleep is significantly increased by clotiazepam. [8]
Clotiazepam has been trialed and found to be effective in the short-term management of anxiety. [9] 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. [10] [11]
A cross-over study in six healthy volunteers (median age 28 years) was conducted using single-dose pharmacokinetics of 5 mg clotiazepam drops, oral tablets, and sublingual tablets. 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. [12]
Similar to other benzodiazepines clotiazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant and muscle relaxant pharmacological properties. [7] 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. [13]
Clotiazepam has a short elimination half-life and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolised via oxidation. [14] 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. [15] 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. [15] In elderly men the elimination half-life is longer and in elderly women the volume of distribution is increased. [16] Individuals with liver impairment have a reduced volume of distribution as well as a reduced total clearance of clotiazepam; renal impairment does not affect the kinetics of clotiazepam. [17]
The dose equivalent to 10 mg diazepam is thought to be between 5 and 10 mg clotiazepam.
Side effects experienced with this product will resemble those of other benzodiazepines. Drowsiness and asthenia are common side effects. [18] There has been a report of reversible hepatitis caused by clotiazepam. [19]
Clotiazepam is a recognised drug of abuse. [20]
Clinical data | |
---|---|
Trade names | Veratran, Rize, Clozan |
AHFS/ Drugs.com | International Drug Names |
Routes of administration | Oral, sublingual, liquid drops |
ATC code | |
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Bioavailability | ~90% |
Metabolism | Hepatic |
Elimination half-life | 4 hours [2] |
Excretion | Renal |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
ECHA InfoCard | 100.046.920 |
Chemical and physical data | |
Formula | C16H15ClN2OS |
Molar mass | 318.82 g·mol−1 |
3D model ( JSmol) | |
| |
| |
(what is this?) (verify) |
Clotiazepam [3] (marketed under brand name Clozan, Distensan, Trecalmo, Rize, Rizen and Veratran) is a thienodiazepine drug which is a benzodiazepine analog. The clotiazepam molecule differs from benzodiazepines in that the benzene ring has been replaced by a thiophene ring. [4] It possesses anxiolytic, [5] skeletal muscle relaxant, [6] anticonvulsant, sedative properties. [7] Stage 2 NREM sleep is significantly increased by clotiazepam. [8]
Clotiazepam has been trialed and found to be effective in the short-term management of anxiety. [9] 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. [10] [11]
A cross-over study in six healthy volunteers (median age 28 years) was conducted using single-dose pharmacokinetics of 5 mg clotiazepam drops, oral tablets, and sublingual tablets. 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. [12]
Similar to other benzodiazepines clotiazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant and muscle relaxant pharmacological properties. [7] 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. [13]
Clotiazepam has a short elimination half-life and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolised via oxidation. [14] 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. [15] 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. [15] In elderly men the elimination half-life is longer and in elderly women the volume of distribution is increased. [16] Individuals with liver impairment have a reduced volume of distribution as well as a reduced total clearance of clotiazepam; renal impairment does not affect the kinetics of clotiazepam. [17]
The dose equivalent to 10 mg diazepam is thought to be between 5 and 10 mg clotiazepam.
Side effects experienced with this product will resemble those of other benzodiazepines. Drowsiness and asthenia are common side effects. [18] There has been a report of reversible hepatitis caused by clotiazepam. [19]
Clotiazepam is a recognised drug of abuse. [20]