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Chemistry

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Also known as: Ativan, 846-49-1, O-chloroxazepam, O-chlorooxazepam, Temesta, Loraz
Molecular Formula
C15H10Cl2N2O2
Molecular Weight
321.2  g/mol
InChI Key
DIWRORZWFLOCLC-UHFFFAOYSA-N
FDA UNII
O26FZP769L

Lorazepam
A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent.
Lorazepam is a Benzodiazepine.
1 2D Structure

Lorazepam

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one
2.1.2 InChI
InChI=1S/C15H10Cl2N2O2/c16-8-5-6-12-10(7-8)13(19-15(21)14(20)18-12)9-3-1-2-4-11(9)17/h1-7,15,21H,(H,18,20)
2.1.3 InChI Key
DIWRORZWFLOCLC-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1=CC=C(C(=C1)C2=NC(C(=O)NC3=C2C=C(C=C3)Cl)O)Cl
2.2 Other Identifiers
2.2.1 UNII
O26FZP769L
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Apo Lorazepam

2. Apo-lorazepam

3. Ativan

4. Donix

5. Duralozam

6. Durazolam

7. Idalprem

8. Laubeel

9. Lorazep Von Ct

10. Lorazepam Medical

11. Lorazepam Neuraxpharm

12. Lorazepam Ratiopharm

13. Lorazepam-neuraxpharm

14. Lorazepam-ratiopharm

15. Medical, Lorazepam

16. Novo Lorazem

17. Novo-lorazem

18. Nu Loraz

19. Nu-loraz

20. Orfidal Wyeth

21. Sedicepan

22. Sinestron

23. Somagerol

24. Tmesta

25. Temesta

26. Tolid

27. Von Ct, Lorazep

28. Wy 4036

29. Wy-4036

30. Wy4036

31. Wyeth, Orfidal

2.3.2 Depositor-Supplied Synonyms

1. Ativan

2. 846-49-1

3. O-chloroxazepam

4. O-chlorooxazepam

5. Temesta

6. Loraz

7. Tavor

8. Delormetazepam

9. Almazine

10. Anxiedin

11. Bonatranquan

12. Duralozam

13. Emotival

14. Lorabenz

15. Sedatival

16. Laubeel

17. Orfidal

18. Punktyl

19. Lorax

20. Quait

21. Wypax

22. Apo-lorazepam

23. Lorazepam Intensol

24. Norlormetazepam

25. Anzepam

26. Aplacasse

27. Azurogen

28. Efasedan

29. Equitam

30. Kalmalin

31. Larpose

32. Lorapam

33. Lorazene

34. Lorazep

35. Lorazin

36. Lorenin

37. Loridem

38. Lorsedal

39. Lozepam

40. Novhepar

41. Renaquil

42. Rocosgen

43. Sedizepan

44. Sidenar

45. Silence

46. Tranqipam

47. Anxira

48. Aripax

49. Bonton

50. Loram

51. Lorat

52. Merlit

53. Stapam

54. Trapax

55. Upan

56. Nervistop L

57. Wy-4036

58. Demethyllormetazepam

59. Lorazepamum

60. Wy 4036

61. (+/-)-lorazepam

62. 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one

63. Lorazepam Preservative Free

64. Lorazepam Civ

65. 2h-1,4-benzodiazepin-2-one, 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-

66. Nsc 289758

67. Idalprem

68. 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2h-1,4-benzodiazepin-2-one

69. Aplacassee

70. Sinestron

71. Donix

72. Tolid

73. Chembl580

74. 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1h-1,4-benzodiazepin-2(3h)-one

75. Lorazepam Medical

76. Nu Loraz

77. 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2h-1,4-benzodiazepin-2-one

78. O26fzp769l

79. Nervistopl

80. Novolorazem

81. Emotion

82. Lomesta

83. Lorafen

84. Lorazon

85. Lorivan

86. Somagerol

87. Vigiten

88. Lorans

89. Lorzem

90. Lopam

91. Lorazepam Fabra

92. Lorazepam-efeka

93. Lorazepan Chobet

94. Lorazepan Richet

95. Max Pax

96. Nsc289758

97. Lorazepam Genericon

98. Lorazepam Lannacher

99. Nsc-289758

100. Ncgc00159439-02

101. Lorsilan

102. Securit

103. Sedazin

104. Pro Dorm

105. 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-2h-1,4-benzodiazepin-2-one

106. 2h-1,4-benzodiazepin-2-one, 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-

107. Lorazepamum [inn-latin]

108. Ativan (tn)

109. Einecs 212-687-6

110. Brn 0759084

111. Unii-o26fzp769l

112. Dea No. 2885

113. Lorazepam [usan:usp:inn:ban:jan]

114. Loreev Xr

115. Lorazepam [inn]

116. Lorazepam [jan]

117. Lorazepam [mi]

118. Lorazepam [usan]

119. (.+/-.)-lorazepam

120. Lorazepam [vandf]

121. Dsstox_cid_3225

122. Lorazepam [mart.]

123. Lorazepam [who-dd]

124. (+-)-7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2h-1,4-benzodiazepin-2-one

125. Dsstox_rid_76932

126. Dsstox_gsid_23225

127. Schembl26961

128. 5-25-02-00248 (beilstein Handbook Reference)

129. Mls001424236

130. Divk1c_000965

131. Lorazepam (jp17/usp/inn)

132. Chebi:6539

133. Gtpl5884

134. Lorazepam [ep Impurity]

135. Lorazepam [orange Book]

136. Lorazepam Civ [usp-rs]

137. Dtxsid7023225

138. Lorazepam [ep Monograph]

139. Hms503a11

140. Kbio1_000965

141. Lorazepam [usp Monograph]

142. Ninds_000965

143. Hms2052h07

144. Hms3394h07

145. Bcp13713

146. Tox21_111669

147. Bdbm50292627

148. Lorazepam 0.1 Mg/ml In Acetonitrile

149. Lorazepam 1.0 Mg/ml In Acetonitrile

150. Akos015904303

151. Ccg-101170

152. Db00186

153. Nc00420

154. 2h-1,4-benzodiazepin-2-one, 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-, (+-)-

155. Idi1_000965

156. Cas-846-49-1

157. Smr000058410

158. Wln: T67 Gmv Jn Ihj Cg Iq Kr Bg

159. L-230

160. D00365

161. 846l491

162. A840886

163. Q408265

164. 7-chloro-5-(o-chlorophenyl)-1,4-benzodiazepin-2-one

165. Brd-a11990600-001-01-8

166. Lorazepam, British Pharmacopoeia (bp) Reference Standard

167. Lorazepam, European Pharmacopoeia (ep) Reference Standard

168. 2h-1, 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-

169. 2h-1, 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-

170. Lorazepam, United States Pharmacopeia (usp) Reference Standard

171. O-chloroxazepam; O-chlorooxazepam; Almazine; Wy 4036; Wy-4036; Wy4036

172. 7-chloranyl-5-(2-chlorophenyl)-3-oxidanyl-1,3-dihydro-1,4-benzodiazepin-2-one

173. 7-chloro-3-hydroxy-5-(2'-chloro-phenyl)-1,3-dihydro-2h-1,4-benzodiazepine-2-one

174. 7-chloro-3-hydroxy-5-(2'-chlorophenyl)-1,3-dihydro-2h-1,4-benzodiazepine-2-one

175. 7-chloro-5-(2-chloro-phenyl)-3-hydroxy-1,3-dihydro-benzo[e][1,4]diazepin-2-one

176. 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2h-1,4-benzodiazepine-2-one

177. 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one.

178. 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-2h-1,4-benzodiazepin-2-one #

179. 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1h-benzo[e][1,4]diazepin-2(3h)-one

180. 7-chloro-5-(2-chlorophenyl)-3-hydroxy-2,3-dihydro-1h-1,4-benzodiazepin-2-one

181. Lorazepam For System Suitability, European Pharmacopoeia (ep) Reference Standard

182. Lorazepam Solution, 1.0 Mg/ml In Acetonitrile, Ampule Of 1 Ml, Certified Reference Material

183. Lorazepam7-chloro-5-(2-chloro-phenyl)-3-hydroxy-1,3-dihydro-benzo[e][1,4]diazepin-2-one

184. (+/-)-7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2h-1,4-benzodiazepin-2-one

185. (rs)-9-chloro-6-(2-chlorophenyl)-4-hydroxy-2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraen-3-one

186. 2h-1,4-benzodiazepin-2-one, 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-, (+/-)-

187. 7-chloro-5-(2-chloro-phenyl)-3-hydroxy-1,3-dihydro-benzo[e][1,4]diazepin-2-one (lorazepam)

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 321.2 g/mol
Molecular Formula C15H10Cl2N2O2
XLogP32.4
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count3
Rotatable Bond Count1
Exact Mass320.0119330 g/mol
Monoisotopic Mass320.0119330 g/mol
Topological Polar Surface Area61.7 Ų
Heavy Atom Count21
Formal Charge0
Complexity443
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 8  
Drug NameAtivan
PubMed HealthLorazepam
Drug ClassesAntianxiety, Anticonvulsant, Skeletal Muscle Relaxant
Drug LabelLorazepam, a benzodiazepine with antianxiety, sedative, and anticonvulsant effects, is intended for the intramuscular or intravenous routes of administration. It has the chemical formula: 7-chloro-5(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1, 4-benzo...
Active IngredientLorazepam
Dosage FormInjectable; Tablet
RouteInjection; Oral
Strength2mg/ml; 4mg/ml; 0.5mg; 2mg; 1mg
Market StatusPrescription
CompanyValeant Intl; Hikma Maple

2 of 8  
Drug NameLorazepam
PubMed HealthLorazepam
Drug ClassesAntianxiety, Anticonvulsant, Skeletal Muscle Relaxant
Drug LabelLorazepam, an antianxiety agent, has the chemical formula, 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one:It is a nearly white powder almost insoluble in water. Each lorazepam tablet, to be taken orally, contains 0.5 mg,...
Active IngredientLorazepam
Dosage FormTablet; Concentrate; Injectable
RouteInjection; Oral
Strength2mg/ml; 0.5mg; 1mg; 4mg/ml; 2mg
Market StatusPrescription
CompanyVintage Pharms; Amneal Pharms; Ranbaxy; Excellium; Hi-tech Pharma; Hospira; Pharm Assoc; Lupin; Sandoz; Watson Labs; Ivax Sub Teva Pharms; Intl Medication Sys; Paddock; Mylan; Akorn

3 of 8  
Drug NameLorazepam intensol
PubMed HealthLorazepam
Drug ClassesAntianxiety, Anticonvulsant, Skeletal Muscle Relaxant
Active IngredientLorazepam
Dosage FormConcentrate
RouteOral
Strength2mg/ml
Market StatusPrescription
CompanyRoxane

4 of 8  
Drug NameLorazepam preservative free
Active IngredientLorazepam
Dosage FormInjectable
RouteInjection
Strength2mg/ml; 4mg/ml
Market StatusPrescription
CompanyBedford Labs

5 of 8  
Drug NameAtivan
PubMed HealthLorazepam
Drug ClassesAntianxiety, Anticonvulsant, Skeletal Muscle Relaxant
Drug LabelLorazepam, a benzodiazepine with antianxiety, sedative, and anticonvulsant effects, is intended for the intramuscular or intravenous routes of administration. It has the chemical formula: 7-chloro-5(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1, 4-benzo...
Active IngredientLorazepam
Dosage FormInjectable; Tablet
RouteInjection; Oral
Strength2mg/ml; 4mg/ml; 0.5mg; 2mg; 1mg
Market StatusPrescription
CompanyValeant Intl; Hikma Maple

6 of 8  
Drug NameLorazepam
PubMed HealthLorazepam
Drug ClassesAntianxiety, Anticonvulsant, Skeletal Muscle Relaxant
Drug LabelLorazepam, an antianxiety agent, has the chemical formula, 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one:It is a nearly white powder almost insoluble in water. Each lorazepam tablet, to be taken orally, contains 0.5 mg,...
Active IngredientLorazepam
Dosage FormTablet; Concentrate; Injectable
RouteInjection; Oral
Strength2mg/ml; 0.5mg; 1mg; 4mg/ml; 2mg
Market StatusPrescription
CompanyVintage Pharms; Amneal Pharms; Ranbaxy; Excellium; Hi-tech Pharma; Hospira; Pharm Assoc; Lupin; Sandoz; Watson Labs; Ivax Sub Teva Pharms; Intl Medication Sys; Paddock; Mylan; Akorn

7 of 8  
Drug NameLorazepam intensol
PubMed HealthLorazepam
Drug ClassesAntianxiety, Anticonvulsant, Skeletal Muscle Relaxant
Active IngredientLorazepam
Dosage FormConcentrate
RouteOral
Strength2mg/ml
Market StatusPrescription
CompanyRoxane

8 of 8  
Drug NameLorazepam preservative free
Active IngredientLorazepam
Dosage FormInjectable
RouteInjection
Strength2mg/ml; 4mg/ml
Market StatusPrescription
CompanyBedford Labs

4.2 Drug Indication

Lorazepam is FDA-approved for the short-term relief of anxiety symptoms related to anxiety disorders and anxiety associated with depressive symptoms such as anxiety-associated insomnia. It is as well used as an anesthesia premedication in adults to relieve anxiety or to produce sedation/amnesia and for the treatment of status epilepticus. Some off-label indications of lorazepam include rapid tranquilization of an agitated patient, alcohol withdrawal delirium, alcohol withdrawal syndrome, muscle spasms, insomnia, panic disorder, delirium, chemotherapy-associated anticipatory nausea and vomiting, and psychogenic catatonia.


FDA Label


5 Pharmacology and Biochemistry
5.1 Pharmacology

The effect of lorazepam in GABA-A receptors produces an increase in the frequency of opening of the chloride ion channel. However, for its effect to generate, the neurotransmitter is required. The anticonvulsant properties of lorazepam are thought to be related to the binding to voltage-dependent sodium channels in which the sustained repetitive firing gets limited by the slow recovery of sodium channels due to the benzodiazepine effect. The effect of lorazepam seems to be very compartmental which was observed with a different generation of sleepiness and a dizziness effect.


5.2 MeSH Pharmacological Classification

Anti-Anxiety Agents

Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here. (See all compounds classified as Anti-Anxiety Agents.)


Antiemetics

Drugs used to prevent NAUSEA or VOMITING. (See all compounds classified as Antiemetics.)


Hypnotics and Sedatives

Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. (See all compounds classified as Hypnotics and Sedatives.)


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
LORAZEPAM
5.3.2 FDA UNII
O26FZP769L
5.3.3 Pharmacological Classes
Benzodiazepines [CS]; Benzodiazepine [EPC]
5.4 ATC Code

N05BA06

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

N05 - Psycholeptics

N05B - Anxiolytics

N05BA - Benzodiazepine derivatives

N05BA06 - Lorazepam


5.5 Absorption, Distribution and Excretion

Absorption

Readily absorbed with an absolute bioavailability of 90% when given orally. When intramuscularly administered a dose of 4 mg, lorazepam is completely and rapidly absorbed and achieves a maximal serum concentration of 48 ng/ml in 15-30 minutes. When administered orally, the time to attained maximum concentration is observed to be of 2 hours.


Route of Elimination

When a single 2 mg oral dose is given to healthy subjects, 88% of the administered dose is recovered in urine and 7% was recovered in feces. From the excreted dose in urine, the major form is the glucuronide version that represents 74% while only 0.3% of the dose is recovered as unchanged lorazepam.


Volume of Distribution

The reported volume of distribution of lorazepam is 1.3 L/kg. It is important to mention that due to the lipophilicity of lorazepam, it does not redistribute as fast in the brain.


Clearance

_In vivo_ studies with lorazepam have shown a clearance rate of 5.8 ml.min/kg.


5.6 Metabolism/Metabolites

Lorazepam is hepatically metabolized by CYP450 isoenzymes and extensively conjugated to the 3-0-phenolic glucuronide. This is an inactive metabolite and is eliminated mainly by the kidneys.


Lorazepam has known human metabolites that include Lorazepam glucuronide.

S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560


5.7 Biological Half-Life

When administered parentally, the registered half-life of lorazepam is of 14 hours.


5.8 Mechanism of Action

Lorazepam allosterically binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane. According to the binding site of lorazepam, we can observe different activities as the binding in the amygdala is known to help mainly in anxiety disorders while the binding in the cerebral cortex helps in seizure disorders.


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12-Jan-2021
31-Oct-2024
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DOSAGE - TABLET;ORAL - 0.5MG

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