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Chemistry

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Also known as: Klonopin, Rivotril, 1622-61-3, Chlonazepam, Antelepsin, Cloazepam
Molecular Formula
C15H10ClN3O3
Molecular Weight
315.71  g/mol
InChI Key
DGBIGWXXNGSACT-UHFFFAOYSA-N
FDA UNII
5PE9FDE8GB

Clonazepam
An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of GAMMA-AMINOBUTYRIC ACID receptor responses.
Clonazepam is a Benzodiazepine.
1 2D Structure

Clonazepam

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
5-(2-chlorophenyl)-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one
2.1.2 InChI
InChI=1S/C15H10ClN3O3/c16-12-4-2-1-3-10(12)15-11-7-9(19(21)22)5-6-13(11)18-14(20)8-17-15/h1-7H,8H2,(H,18,20)
2.1.3 InChI Key
DGBIGWXXNGSACT-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1C(=O)NC2=C(C=C(C=C2)[N+](=O)[O-])C(=N1)C3=CC=CC=C3Cl
2.2 Other Identifiers
2.2.1 UNII
5PE9FDE8GB
2.3 Synonyms
2.3.1 MeSH Synonyms

1. 2h-1,4-benzodiazepin-2-one, 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-

2. Antelepsin

3. Klonopin

4. Rivotril

5. Ro 5-4023

6. Ro 54023

2.3.2 Depositor-Supplied Synonyms

1. Klonopin

2. Rivotril

3. 1622-61-3

4. Chlonazepam

5. Antelepsin

6. Cloazepam

7. Iktorivil

8. Clonazepamum

9. Clonopin

10. Landsen

11. Antilepsin

12. Lonazep

13. Kenoket

14. Ravotril

15. Rivatril

16. Clonex

17. Paxam

18. Ro 5-4023

19. Ro 4-8180

20. 5-(2-chlorophenyl)-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one

21. 2h-1,4-benzodiazepin-2-one, 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-

22. Clonazepam Civ

23. 1,3-dihydro-7-nitro-5-(2-chlorophenyl)-2h-1,4.benzodiazepin-2-one

24. 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2h-1,4-benzodiazepin-2-one

25. 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2h-1,4-benzodiazepin-2-one

26. Nsc 179913

27. Ro-5-4023

28. 7-nitro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2(1h)-one

29. Ro-54023

30. 5pe9fde8gb

31. Chembl452

32. Nsc-179913

33. 5-(2-chlorophenyl)-7-nitro-1,3-dihydro-2h-1,4-benzodiazepin-2-one

34. 2h-1,4-benzodiazepin-2-one, 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-

35. Chebi:3756

36. Lktorivil

37. Solfidin

38. Alti-clonazepam

39. 5-(o-chlorophenyl)-7-nitro-1,3-dihydro-2h-1,4-benzodiazepin-2-one

40. 5-(2-chloro-phenyl)-7-nitro-1,3-dihydro-benzo[e][1,4]diazepin-2-one

41. Nsc179913

42. Melzap

43. 2-h-1,4-benzodiazepin-2-one, 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-

44. Klonopin Rapidly Disintegrating

45. Clonazepamum [inn-latin]

46. Apetryl

47. 5-(2-chlorophenyl)-7-nitro-1h-benzo[e][1,4]diazepin-2(3h)-one

48. Klonopin (tn)

49. Ro 54023

50. Ro 5-4023/b-7

51. Hsdb 3265

52. Einecs 216-596-2

53. Unii-5pe9fde8gb

54. Brn 0759557

55. Dea No. 2737

56. 5-(o-chlorophenyl)-7-nitro-1h-1,4-benzodiazepin-2(3h)-one

57. Clonazepam, Powder

58. Ro 4023

59. Ro4023

60. Clonazepam [usan:usp:inn:ban:jan]

61. Clonazepam [mi]

62. Clonazepam [inn]

63. Clonazepam [jan]

64. Clonazepam [hsdb]

65. Clonazepam [usan]

66. 1,4.benzodiazepin-2-one

67. Clonazepam [vandf]

68. Clonazepam [mart.]

69. Clonazepam [who-dd]

70. Bidd:pxr0144

71. Oprea1_168772

72. Schembl38899

73. 5-24-04-00351 (beilstein Handbook Reference)

74. Mls003899214

75. Divk1c_000973

76. Clonazepam (jp17/usp/inn)

77. Gtpl6963

78. Clonazepam [orange Book]

79. Clonazepam Civ [usp-rs]

80. Dtxsid1022845

81. Niosh/df2374250

82. Clonazepam--dea Schedule Iv Item

83. Hms503c07

84. Kbio1_000973

85. Clonazepam [ep Monograph]

86. Ninds_000973

87. Clonazepam [usp Monograph]

88. Hms2093h22

89. Clonazepam 0.1 Mg/ml In Methanol

90. Clonazepam 1.0 Mg/ml In Methanol

91. Zinc3813003

92. 1,3-dihydro-5-(o-chlorophenyl)-7-nitro-3h-1,4-benzodiazepin-2-one

93. Bdbm50019213

94. Akos015902192

95. Ccg-213669

96. Db01068

97. Idi1_000973

98. Wln: T67 Gmv Jn Ihj Cnw Kr Bg

99. 106955-87-7

100. Ac-15733

101. Smr000058982

102. Sbi-0206863.p001

103. Df23742500

104. 5-(2-chlorophenyl)-1,4-benzodiazepin-2-one

105. 5-(o-chlorophenyl)-1,4-benzodiazepin-2-one

106. D00280

107. Ab01563349_01

108. 622c613

109. A810362

110. Q407988

111. Sr-01000937610

112. 2-h-1, 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-

113. 2h-1, 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-

114. 2h-1, 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-

115. Sr-01000937610-2

116. Clonazepam Solution, Drug Standard, 1.0 Mg/ml In Methanol

117. Clonazepam, European Pharmacopoeia (ep) Reference Standard

118. 3h-1,4-benzodiazepin-2-one, 1,3-dihydro-5-(o-chlorophenyl)-7-nitro-

119. 5-(2-chlorophenyl)-7-nitro-1,3-dihydro-2h-1,4-benzodiazepin-2-one #

120. 5-(2-chlorophenyl)-7-nitro-2,3-dihydro-1h-1,4-benzodiazepin-2-one

121. 7-nitro-1,3-dihydro-5-(o-chlorophenyl)-2h-1,4-benzodiazepin-2-one

122. Clonazepam Solution, 1.0 Mg/ml In Methanol, Ampule Of 1 Ml, Certified Reference Material

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 315.71 g/mol
Molecular Formula C15H10ClN3O3
XLogP32.4
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count4
Rotatable Bond Count1
Exact Mass315.0410689 g/mol
Monoisotopic Mass315.0410689 g/mol
Topological Polar Surface Area87.3 Ų
Heavy Atom Count22
Formal Charge0
Complexity491
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 4  
Drug NameClonazepam
PubMed HealthClonazepam (By mouth)
Drug ClassesAntianxiety, Anticonvulsant
Drug LabelClonazepam, USP a benzodiazepine, is available for oral administration as scored tablets containing 0.5 mg, 1 mg or 2 mg of clonazepam. In addition, each tablet also contains the following inactive ingredients: corn starch, lactose monohydrate, magne...
Active IngredientClonazepam
Dosage FormTablet, orally disintegrating; Tablet
RouteOral
Strength0.5mg; 2mg; 1mg; 0.25mg; 0.125mg
Market StatusPrescription
CompanyWatson Labs; Vintage Pharms; Mylan Pharms; Actavis Elizabeth; Teva; Accord Hlthcare; Sun Pharm Inds; Sandoz; Par Pharm; Mylan; Barr

2 of 4  
Drug NameKlonopin
PubMed HealthClonazepam (By mouth)
Drug ClassesAntianxiety, Anticonvulsant
Drug LabelKlonopin, a benzodiazepine, is available as scored tablets with a K-shaped perforation containing 0.5 mg of clonazepam and unscored tablets with a K-shaped perforation containing 1 mg or 2 mg of clonazepam. Each tablet also contains lactose, magnesiu...
Active IngredientClonazepam
Dosage FormTablet
RouteOral
Strength0.5mg; 1mg; 2mg
Market StatusPrescription
CompanyRoche

3 of 4  
Drug NameClonazepam
PubMed HealthClonazepam (By mouth)
Drug ClassesAntianxiety, Anticonvulsant
Drug LabelClonazepam, USP a benzodiazepine, is available for oral administration as scored tablets containing 0.5 mg, 1 mg or 2 mg of clonazepam. In addition, each tablet also contains the following inactive ingredients: corn starch, lactose monohydrate, magne...
Active IngredientClonazepam
Dosage FormTablet, orally disintegrating; Tablet
RouteOral
Strength0.5mg; 2mg; 1mg; 0.25mg; 0.125mg
Market StatusPrescription
CompanyWatson Labs; Vintage Pharms; Mylan Pharms; Actavis Elizabeth; Teva; Accord Hlthcare; Sun Pharm Inds; Sandoz; Par Pharm; Mylan; Barr

4 of 4  
Drug NameKlonopin
PubMed HealthClonazepam (By mouth)
Drug ClassesAntianxiety, Anticonvulsant
Drug LabelKlonopin, a benzodiazepine, is available as scored tablets with a K-shaped perforation containing 0.5 mg of clonazepam and unscored tablets with a K-shaped perforation containing 1 mg or 2 mg of clonazepam. Each tablet also contains lactose, magnesiu...
Active IngredientClonazepam
Dosage FormTablet
RouteOral
Strength0.5mg; 1mg; 2mg
Market StatusPrescription
CompanyRoche

4.2 Therapeutic Uses

Anticonvulsants; GABA Modulators

National Library of Medicine's Medical Subject Headings. Clonazepam. Online file (MeSH, 2017). Available from, as of October 2, 2017: https://meshb.nlm.nih.gov/search


/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Clonazepam is included in the database.

NIH/NLM; ClinicalTrials.Gov. Available from, as of October 2, 2017: https://clinicaltrials.gov/


Klonopin is useful alone or as an adjunct in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic and myoclonic seizures. In patients with absence seizures (petit mal) who have failed to respond to succinimides, Klonopin may be useful. /Included in US product label/

US Natl Inst Health; DailyMed. Current Medication Information for Klonopin (Clonazepam) Tablet (July 2017). Available from, as of October 9, 2017: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=542f22e8-dad2-47a8-93b6-30936715d73b


Klonopin is indicated for the treatment of panic disorder, with or without agoraphobia, as defined in DSM-IV. Panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks. /Included in US product label/

US Natl Inst Health; DailyMed. Current Medication Information for Klonopin (Clonazepam) Tablet (July 2017). Available from, as of October 9, 2017: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=542f22e8-dad2-47a8-93b6-30936715d73b


For more Therapeutic Uses (Complete) data for Clonazepam (11 total), please visit the HSDB record page.


4.3 Drug Warning

/BOXED WARNING/ WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

US Natl Inst Health; DailyMed. Current Medication Information for Klonopin (Clonazepam) Tablet (July 2017). Available from, as of October 9, 2017: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=542f22e8-dad2-47a8-93b6-30936715d73b


Klonopin should not be used in patients with a history of sensitivity to benzodiazepines, nor in patients with clinical or biochemical evidence of significant liver disease. It may be used in patients with open angle glaucoma who are receiving appropriate therapy but is contraindicated in acute narrow angle glaucoma.

US Natl Inst Health; DailyMed. Current Medication Information for Klonopin (Clonazepam) Tablet (July 2017). Available from, as of October 9, 2017: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=542f22e8-dad2-47a8-93b6-30936715d73b


Benzodiazepines have the potential to impair judgment, thinking, or motor skills. Therefore, patients receiving clonazepam should be cautioned that the drug may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) and to avoid such activities until they experience how the drug affects them.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017, p. 2339


Clinical studies of Klonopin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Because clonazepam undergoes hepatic metabolism, it is possible that liver disease will impair clonazepam elimination. Metabolites of Klonopin are excreted by the kidneys; to avoid their excess accumulation, caution should be exercised in the administration of the drug to patients with impaired renal function. Because elderly patients are more likely to have decreased hepatic and/or renal function, care should be taken in dose selection, and it may be useful to assess hepatic and/or renal function at the time of dose selection. Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of Klonopin and observed closely.

US Natl Inst Health; DailyMed. Current Medication Information for Klonopin (Clonazepam) Tablet (July 2017). Available from, as of October 9, 2017: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=542f22e8-dad2-47a8-93b6-30936715d73b


For more Drug Warnings (Complete) data for Clonazepam (30 total), please visit the HSDB record page.


4.4 Drug Indication

Clonazepam is indicated as monotherapy or as an adjunct in the treatment of Lennox-Gastaut syndrome (petit mal variant), akinetic, and myoclonic seizures. Furthermore, clonazepam may also be of some value in patients with absence spells (petit mal) who have failed to respond to succinimides. Additionally, clonazepam is also indicated for the treatment of panic disorder, with or without agoraphobia, as defined in the DSM-V. 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. 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.


FDA Label


5 Pharmacology and Biochemistry
5.1 Pharmacology

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. Moreover, the agent can also decrease the frequency, amplitude, duration, and spread of discharge in minor motor seizures. 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.


5.2 MeSH Pharmacological Classification

Anticonvulsants

Drugs used to prevent SEIZURES or reduce their severity. (See all compounds classified as Anticonvulsants.)


GABA Modulators

Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here. (See all compounds classified as GABA Modulators.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
CLONAZEPAM
5.3.2 FDA UNII
5PE9FDE8GB
5.3.3 Pharmacological Classes
Benzodiazepines [CS]; Benzodiazepine [EPC]
5.4 ATC Code

N03AE01

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


N - Nervous system

N03 - Antiepileptics

N03A - Antiepileptics

N03AE - Benzodiazepine derivatives

N03AE01 - Clonazepam


5.5 Absorption, Distribution and Excretion

Absorption

Clonazepam is rapidly and almost entirely absorbed after oral administration as tablets. 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. The absolute bioavailability is approximately 90% - but with substantially large differences between individuals.


Route of Elimination

Approximately 50-70% of a clonazepam dose is excreted in the urine and 10-30% is excreted in the feces as metabolites. The excretion of unchanged clonazepam in the urine is typically less than 2% of the administered dose. Metabolites of clonazepam are present in urine as both free and conjugated (glucuronide and sulfate) compounds.


Volume of Distribution

Clonazepam distributes very rapidly to various organs and body tissues with preferential uptake by brain structures. The apparent volume of distribution has been documented as approximately 3 L/kg.


Clearance

The documented clearance for clonazepam is approximately 55 ml/min regardless of gender. Nevertheless, clearance values normalized by weight decline with increasing body weight.


/MILK/ A 2750-g female infant was born at 36 weeks' gestation to a 40-year-old woman treated with clonazepam throughout her pregnancy. The infant developed apnea, cyanosis, and hypotonia within a few hours of birth. The mother's serum clonazepam level at delivery was 32 ng/mL; the cord blood level was 19 ng/mL. The infant had no congenital malformations, evidence of infection, or seizures. Clinical episodes ceased by ten days of age. The woman elected to breastfeed; breast milk clonazepam levels were between 11 and 13 ng/mL. She was discharged with a cardiorespiratory monitor. The authors suggest that infants of mothers receiving this agent during pregnancy or while nursing have serum levels measured. Additionally, these infants should be monitored for central nervous system depression or apnea.

PMID:4022513 Fisher JB et al; Obstet Gynecol 66 (3 Suppl): 34S-35S (1985)


Clonazepam is rapidly and well absorbed from the GI tract. The absolute bioavailability is approximately 90%. In one study, peak blood concentrations of 6.5-13.5 ng/mL were usually reached within 1-2 hours following a single 2 mg oral dose of micronized clonazepam in healthy adults. In some individuals, however, peak blood concentrations were reached at 4-8 hours. Although the plasma concentration of clonazepam required for anticonvulsant effects has not been definitely established, some studies indicate it may be 20-80 ng/mL. Plasma concentrations in this range have been reported to be maintained in adults receiving 6 mg of clonazepam daily in 3 divided doses and in children 6-13 years of age receiving 1.5-4 mg of the drug daily in 3 divided doses. The onset of anticonvulsant action usually occurs within 20-60 minutes, and the duration of action usually is 6-8 hours in infants and young children and up to 12 hours in adults.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017, p. 2340


There is little information on the distribution of clonazepam. Clonazepam is approximately 85% bound to plasma proteins. Like other benzodiazepines, the drug apparently crosses the blood-brain barrier and the placenta.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017, p. 2340


Clonazepam is extensively metabolized in the liver to several metabolites ... . Only very small amounts of the drug (less than 2%) are excreted unchanged.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017, p. 2340


For more Absorption, Distribution and Excretion (Complete) data for Clonazepam (6 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

Clonazepam is metabolized principally in the liver. The metabolic pathways include hydroxylation, reduction of the nitro groups to amine groups, and the addition of acetate to the amino grouping. In particular, clonazepam is extensively metabolized by reduction to 7-amino-clonazepam and by N-acetylation to 7-acetamido-clonazepam. Hydroxylation at the C-3 position also occurs. Hepatic cytochrome P450 3A4 is implicated in the nitroreduction of clonazepam to pharmacologically inactive metabolites.


The shortcomings of clonazepam therapy include tolerance, withdrawal symptoms, and adverse effects such as drowsiness, dizziness, and confusion leading to increased risk of falls. Inter-individual variability in the incidence of adverse events in patients partly originates from the differences in clonazepam metabolism due to genetic and nongenetic factors. Since the prominent role in clonazepam nitro-reduction and acetylation of 7-amino-clonazepam is assigned to CYP3A and N-acetyl transferase 2 enzymes, respectively, the association between the patients' CYP3A status (CYP3A5 genotype, CYP3A4 expression) or N-acetyl transferase 2 acetylator phenotype and clonazepam metabolism (plasma concentrations of clonazepam and 7-amino-clonazepam) was evaluated in 98 psychiatric patients suffering from schizophrenia or bipolar disorders. The patients' CYP3A4 expression was found to be the major determinant of clonazepam plasma concentrations normalized by the dose and bodyweight (1263.5 +/- 482.9 and 558.5 +/- 202.4 ng/mL per mg/kg bodyweight in low and normal expressers, respectively, P<0.0001). Consequently, the dose requirement for the therapeutic concentration of clonazepam was substantially lower in low-CYP3A4 expresser patients than in normal expressers (0.029 +/- 0.011 vs 0.058 +/- 0.024 mg/kg bodyweight, P<0.0001). Furthermore, significantly higher (about 2-fold) plasma concentration ratio of 7-amino-clonazepam and clonazepam was observed in the patients displaying normal CYP3A4 expression and slower N-acetylation than all the others. Prospective assaying of CYP3A4 expression and N-acetyl transferase 2 acetylator phenotype can better identify the patients with higher risk of adverse reactions and can facilitate the improvement of personalized clonazepam therapy and withdrawal regimen.

PMID:27639091 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203763 Toth K et al; Int J Neuropsychopharmacol. 2016 Dec 30;19(12). pii: pyw083. doi: 10.1093/ijnp/pyw083.


Clonazepam is extensively metabolized in the liver to several metabolites including 7-aminoclonazepam, 7-acetaminoclonazepam, and 3-hydroxy derivatives of these metabolites and clonazepam. Clonazepam metabolites are excreted in urine by first-order kinetics, principally as their glucuronide and/or sulfate conjugates.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017, p. 2340


5.7 Biological 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.


Elimination half-life ... 18.7 to 39 hr.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017, p. 2340


5.8 Mechanism of Action

Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body. 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. 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. Subsequently, benzodiazepines like clonazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors. 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. 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. 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. 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. 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. 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.


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30-Jan-2021
29-Oct-2024
KGS
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Quantity (KGS) & Unit rate (USD/KGS) over time

API Imports and Exports

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DOSAGE - TABLET;ORAL - 0.5MG

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