Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | 2C6H8ClNS.C2H6O6S2 |
| Molecular Weight | 513.5 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=C(CCCl)SC=N1.CC2=C(CCCl)SC=N2.OS(=O)(=O)CCS(O)(=O)=O
InChI
InChIKey=WFVBVWRCFZCWJU-UHFFFAOYSA-N
InChI=1S/2C6H8ClNS.C2H6O6S2/c2*1-5-6(2-3-7)9-4-8-5;3-9(4,5)1-2-10(6,7)8/h2*4H,2-3H2,1H3;1-2H2,(H,3,4,5)(H,6,7,8)
| Molecular Formula | C2H6O6S2 |
| Molecular Weight | 190.195 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C6H8ClNS |
| Molecular Weight | 161.652 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Chlormethiazole has sedative, hypnotic, anticonvulsant and neuroprotective properties. This drug is approved in different counties under the different brand name (e.g., Heminevrin) and is used for the management of restlessness and agitation in the elderly, short-term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms. Clomethiazole interacts with the picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex. Clomethiazole is pharmacologically distinct from both the benzodiazepines and the barbiturates. Given alone its effects on respiration are slight and the therapeutic index high.
CNS Activity
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex Sources: https://www.ncbi.nlm.nih.gov/pubmed/2544811 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Heminevrin Approved UseClomethiazole is a short acting hypnotic and sedative with anticonvulsant effect. It is used for the: management of restlessness and agitation in the elderly, short term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms where close hospital supervision is also provided. |
|||
| Primary | Heminevrin Approved UseClomethiazole is a short acting hypnotic and sedative with anticonvulsant effect. It is used for the: management of restlessness and agitation in the elderly, short term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms where close hospital supervision is also provided. |
|||
| Primary | Heminevrin Approved UseClomethiazole is a short acting hypnotic and sedative with anticonvulsant effect. It is used for the: management of restlessness and agitation in the elderly, short term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms where close hospital supervision is also provided. |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.55 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10397378/ |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOMETHIAZOLE serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.4 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10397378/ |
600 mg single, rectal dose: 600 mg route of administration: Rectal experiment type: SINGLE co-administered: |
CLOMETHIAZOLE serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
40 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12734608/ |
265 μmol/kg single, intravenous dose: 265 μmol/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
33 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12734608/ |
265 μmol/kg single, intravenous dose: 265 μmol/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
39 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12734608/ |
265 μmol/kg single, intravenous dose: 265 μmol/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.95 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
192 mg single, oral dose: 192 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
0.27 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
192 mg single, oral dose: 192 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
110.8 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10397378/ |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOMETHIAZOLE serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
73.2 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10397378/ |
600 mg single, rectal dose: 600 mg route of administration: Rectal experiment type: SINGLE co-administered: |
CLOMETHIAZOLE serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
224 mg × min/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
162 mg single, intravenous dose: 162 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
149 mg × min/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
162 mg single, intravenous dose: 162 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
303 mg × min/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
192 mg single, oral dose: 192 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
17.5 mg × min/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
192 mg single, oral dose: 192 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
10 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12734608/ |
265 μmol/kg single, intravenous dose: 265 μmol/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12734608/ |
265 μmol/kg single, intravenous dose: 265 μmol/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12734608/ |
265 μmol/kg single, intravenous dose: 265 μmol/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
162 mg single, intravenous dose: 162 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
6.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
162 mg single, intravenous dose: 162 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
8.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
192 mg single, oral dose: 192 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
44.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
CLOMETHIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
||
35.6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6995129/ |
CLOMETHIAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
390 mg single, oral Studied dose |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
|
390 mg single, rectal Studied dose Dose: 390 mg Route: rectal Route: single Dose: 390 mg Sources: |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
|
75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Somnolence... Other AEs: Somnolence, Rhinitis... AEs leading to discontinuation/dose reduction: Somnolence (15.6%) Other AEs:Somnolence (53%) Sources: Rhinitis (19%) Fever (17%) Headache (12%) Hypertension (8%) Coughing (7%) Yawning (7%) Sputum increased (5%) Agitation (5%) Somnolence (3%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Headache | 12% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Somnolence | 15.6% Disc. AE |
75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Fever | 17% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Rhinitis | 19% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Somnolence | 3% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Agitation | 5% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Sputum increased | 5% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Somnolence | 53% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Coughing | 7% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Yawning | 7% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Hypertension | 8% | 75 mg/kg single, intravenous Studied dose Dose: 75 mg/kg Route: intravenous Route: single Dose: 75 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Inhibition of cytochrome P4502E1 by chlormethiazole attenuated acute ethanol-induced fatty liver. | 2014-10-05 |
|
| CMZ reversed chronic ethanol-induced disturbance of PPAR-α possibly by suppressing oxidative stress and PGC-1α acetylation, and activating the MAPK and GSK3β pathway. | 2014 |
|
| Ethanol induction of CYP2A5: role of CYP2E1-ROS-Nrf2 pathway. | 2012-08 |
|
| Sulforaphane prevents microcystin-LR-induced oxidative damage and apoptosis in BALB/c mice. | 2011-08-15 |
|
| Low effective organizational strategies in visual memory performance of unmedicated alcoholics during early abstinence. | 2010-12-14 |
|
| Impaired cerebral autoregulation during acute alcohol withdrawal. | 2010-08-01 |
|
| Medications acting on the GABA system in the treatment of alcoholic patients. | 2010 |
|
| An open trial of gabapentin in acute alcohol withdrawal using an oral loading protocol. | 2009-12-19 |
|
| Characterization of cardamonin metabolism by P450 in different species via HPLC-ESI-ion trap and UPLC-ESI-quadrupole mass spectrometry. | 2009-10 |
|
| Oxcarbazepine in combination with Tiaprid in inpatient alcohol-withdrawal--a RCT. | 2009-09 |
|
| Gamma hydroxybutyric acid (GHB) for the treatment of alcohol dependence: a review. | 2009-06 |
|
| [Pharmacotherapy of substance dependence and withdrawal syndromes]. | 2009-06 |
|
| [Anticonvulsants in the treatment of alcoholism]. | 2009-04 |
|
| [Use of combined treatment with melatonin and clomethiazole in circadian rhythm sleep disorder in the elderly with dementia]. | 2009-01-19 |
|
| Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines. | 2009 |
|
| Gamma-hydroxybutyric acid versus clomethiazole for the treatment of alcohol withdrawal syndrome in a medical intensive care unit: an open, single-center randomized study. | 2009 |
|
| A comprehensive functional analysis of tissue specificity of human gene expression. | 2008-11-12 |
|
| Treatment with clomethiazole is associated with lower rates of premature discharge during alcohol withdrawal. | 2008-07 |
|
| Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury. | 2008 |
|
| The effectiveness of anticonvulsants in psychiatric disorders. | 2008 |
|
| Angiogenesis as a predictive marker of neurological outcome following hypoxia-ischemia. | 2007-09-26 |
|
| Clinical studies with oral lipid based formulations of poorly soluble compounds. | 2007-08 |
|
| AMPA receptor activation reduces epileptiform activity in the rat neocortex. | 2007-07-16 |
|
| Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study. | 2007-07 |
|
| Measurement properties of the National Institutes of Health Stroke Scale for people with right- and left-hemisphere lesions: further analysis of the clomethiazole for acute stroke study-ischemic (class-I) trial. | 2007-03 |
|
| Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration. | 2007-01-19 |
|
| [Carbamazepine intoxication. Complication of alcohol detoxification with combined carbamazepine and tiapride]. | 2007-01 |
|
| Reduced baroreflex sensitivity in acute alcohol withdrawal syndrome and in abstained alcoholics. | 2006-10-15 |
|
| Heart rate variability and sympathetic skin response in male patients suffering from acute alcohol withdrawal syndrome. | 2006-09 |
|
| Modeling drug- and system-related changes in body temperature: application to clomethiazole-induced hypothermia, long-lasting tolerance development, and circadian rhythm in rats. | 2006-04 |
|
| Ubiquitin-dependent degradation of p53 protein despite phosphorylation at its N terminus by acetaminophen. | 2006-04 |
|
| Chorea induced by low-dose trazodone. | 2006 |
|
| Methodological quality of animal studies on neuroprotection in focal cerebral ischaemia. | 2005-09 |
|
| Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal. | 2005-09 |
|
| Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus. | 2005-08-22 |
|
| The effects of clomethiazole on polysomnographically recorded sleep in healthy subjects. | 2005-08 |
|
| Clomethiazole: mechanisms underlying lasting neuroprotection following hypoxia-ischemia. | 2005-06 |
|
| Rapid and long-lasting tolerance to clomethiazole-induced hypothermia in the rat. | 2005-04-11 |
|
| Alcohol, vitamin A, and cancer. | 2005-04 |
|
| Treatment of alcohol withdrawal syndrome with combined carbamazepine and tiapride in a patient with probable sleep apnoe syndrome. | 2005-03 |
|
| Generic three-column parallel LC-MS/MS system for high-throughput in vitro screens. | 2004-11-26 |
|
| Factor analysis of the National Institutes of Health Stroke Scale in patients with large strokes. | 2004-11 |
|
| Polysomnography during withdrawal with clomethiazole or placebo in alcohol dependent patients--a double-blind and randomized study. | 2004-09 |
|
| Inhibition of CYP2E1 activity does not abolish pulsatile urine alcohol concentrations during chronic alcohol infusions. | 1995-06-15 |
|
| Sudden death after intravenous application of lorazepam in a patient treated with clozapine. | 1994-05 |
|
| Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine. | 1993-03 |
|
| A single-dose study of the pharmacodynamic effects of chlormethiazole, temazepam and placebo in elderly parkinsonian patients. | 1991-11 |
|
| Focal dystonic reaction to phenytoin. | 1984-10 |
|
| Anticonvulsant-induced status epilepticus in Lennox-Gastaut syndrome. | 1981-02 |
|
| Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia. | 1979-01 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.medicines.org.uk/emc/medicine/33156
Management of restlessness and agitation in the elderly: one capsule three times daily.
Severe insomnia in the elderly: 1 - 2 capsules before going to bed. The lower dose should be tried first. As with all psychotropic drugs, treatment should be kept to a minimum, reviewed regularly and discontinued as soon as possible.
Alcohol withdrawal states: Clomethiazole is not a specific 'cure' for alcoholism. Alcohol withdrawal should be treated in hospital or, in exceptional circumstances, on an outpatient basis by specialist units when the daily dosage of clomethiazole must be monitored closely by community health staff. The dosage should be adjusted to patient response. The patient should be sedated but rousable. A suggested regimen is:
Initial dose:
Day 1, first 24 hours:
Day 2:
Day 3:
Days 4 to 6: 2 to 4 capsules, if necessary repeated after some hours.
9 to 12 capsules, divided into 3 or 4 doses.
6 to 8 capsules, divided into 3 or 4 doses.
4 to 6 capsules, divided into 3or 4 doses.
A gradual reduction in dosage until the final dose.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11082484
Using in vitro grease-gap recordings, it was shown that chlormethiazole inhibited epileptiform activity in neocortical slices superfused with Mg(2+)-free medium (IC(50) approximately 200 microM). At an antiepileptic concentration (300 microM), chlormethiazole potentiated the action of exogenously applied GABA (1 mM) but did not affect responses to the glutamate receptor agonists N-methyl-D-aspartate (10 microM) or L-quisqualic acid (3 microM). The GABA(A) receptor antagonist N-methyl-bicuculline (50 microM) reduced chlormethiazole's potency to inhibit the epileptiform activity. These results indicated that chlormethiazole's anticonvulsant action was likely mediated by potentiating GABA(A)ergic inhibition rather than by antagonising glutamatergic excitation.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 17:48:58 GMT 2025
by
admin
on
Mon Mar 31 17:48:58 GMT 2025
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| Record UNII |
22NJI0W1D2
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| Record Status |
Validated (UNII)
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| Record Version |
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-
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100000085629
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C034739
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20802
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1867-58-9
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22NJI0W1D2
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m3645
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9892648
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DTXSID40940133
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SUB01358MIG
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217-483-0
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