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Technical details about Prestwick2_000921, learn more about the structure, uses, toxicity, action, side effects and more

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2D Structure
Also known as: 76963-41-2, Axid, Zanizal, Nizax, Ly-139037, Niaztidine
Molecular Formula
C12H21N5O2S2
Molecular Weight
331.5  g/mol
InChI Key
SGXXNSQHWDMGGP-IZZDOVSWSA-N

A histamine H2 receptor antagonist with low toxicity that inhibits gastric acid secretion. The drug is used for the treatment of duodenal ulcers.
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(E)-1-N'-[2-[[2-[(dimethylamino)methyl]-1,3-thiazol-4-yl]methylsulfanyl]ethyl]-1-N-methyl-2-nitroethene-1,1-diamine
2.1.2 InChI
InChI=1S/C12H21N5O2S2/c1-13-11(6-17(18)19)14-4-5-20-8-10-9-21-12(15-10)7-16(2)3/h6,9,13-14H,4-5,7-8H2,1-3H3/b11-6+
2.1.3 InChI Key
SGXXNSQHWDMGGP-IZZDOVSWSA-N
2.1.4 Canonical SMILES
CNC(=C[N+](=O)[O-])NCCSCC1=CSC(=N1)CN(C)C
2.1.5 Isomeric SMILES
CN/C(=C\[N+](=O)[O-])/NCCSCC1=CSC(=N1)CN(C)C
2.2 Synonyms
2.2.1 MeSH Synonyms

1. Axid

2. Ly 139037

3. Ly-139037

4. Ly139037

5. N-(2-(((2-((dimethylamino)methyl)-4-thiazolyl)methyl)thio)ethyl)-n'-methyl-2-nitro-1,1-ethenediamine

2.2.2 Depositor-Supplied Synonyms

1. 76963-41-2

2. Axid

3. Zanizal

4. Nizax

5. Ly-139037

6. Niaztidine

7. Nizatidinum

8. Nizatidina

9. Ze-101

10. Zl-101

11. (e)-n-(2-(((2-((dimethylamino)methyl)thiazol-4-yl)methyl)thio)ethyl)-n'-methyl-2-nitroethene-1,1-diamine

12. (e)-n-(2-(((2-((dimethylamino)methyl)thiazol-4-yl)methyl)thio)ethyl)-n-methyl-2-nitroethene-1,1-diamine

13. Dimethyl[(4-{[(2-{[(e)-1-(methylamino)-2-nitroethenyl]amino}ethyl)sulfanyl]methyl}-1,3-thiazol-2-yl)methyl]amine

14. N-(4-(6-methylamino-7-nitro-2-thia-5-aza-6-hepten-1-yl)-2-thiazolylmethyl)-n,n-dimethylamine

15. Smr000466384

16. Acinon (tn)

17. Axid (tn)

18. Chebi:7601

19. Mfcd00865660

20. Ncgc00016934-01

21. Cas-76963-41-2

22. Prestwick2_000921

23. Schembl769

24. Schembl770

25. Chembl653

26. Ly-139037, Nizatidine

27. Mls000759518

28. Mls001076680

29. Mls001424001

30. Bidd:gt0761

31. Nizatidine, Analytical Standard

32. Gtpl7248

33. Nizatidine (jp17/usp/inn)

34. Nizatidine For System Suitability

35. Hms2051k04

36. Hms2094a15

37. Hms2235n05

38. Pharmakon1600-01505985

39. Hy-b0310

40. Zinc1530736

41. Nsc759289

42. Akos015900643

43. Ac-5272

44. Ccg-100836

45. Db00585

46. Hs-0083

47. Nc00086

48. Ncgc00016934-02

49. (e)-n-{2-[({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)thio]ethyl}-n'-methyl-2-nitroethene-1,1-diamine

50. Bn166185

51. Sbi-0206937.p001

52. C07270

53. D00440

54. Ab00698253-07

55. Ab00698253_09

56. Benzenesulfonylchloride,4-hydroxy-3-nitro-(9ci)

57. 963n412

58. A838919

59. L000761

60. Sr-01000765410

61. Q1188290

62. Sr-01000765410-4

63. Brd-k73589491-001-05-4

64. Brd-k92193792-001-01-7

65. (e)-1-n'-[2-[[2-[(dimethylamino)methyl]-1,3-thiazol-4-yl]methylsulfanyl]ethyl]-1-n-methyl-2-nitroethene-1,1-diamine

66. (e)-n-(2-((2-((dimethylamino)methyl)thiazol-4-yl)methylthio)ethyl)-n-methyl-2-nitroethene-1,1-diamine

67. (e)-n1'-[2-[[2-[(dimethylamino)methyl]-1,3-thiazol-4-yl]methylsulfanyl]ethyl]-n1-methyl-2-nitro-ethene-1,1-diamine

68. (e)-n1'-[2-[[2-[(dimethylamino)methyl]-4-thiazolyl]methylthio]ethyl]-n1-methyl-2-nitroethene-1,1-diamine

69. 1,1-ethenediamine, N'-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-n-methyl-2-nitro-

70. N-(2-(((2-((dimethylamino)methyl)thiazol-4-yl)methyl)thio)ethyl)-n-methyl-2-nitroethene-1,1-diamine

71. N-{2-[({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)sulfanyl]ethyl}-n'-methyl-2-nitroethene-1,1-diamine

2.3 Create Date
2005-06-24
3 Chemical and Physical Properties
Molecular Weight 331.5 g/mol
Molecular Formula C12H21N5O2S2
XLogP31.6
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count8
Rotatable Bond Count9
Exact Mass331.11366728 g/mol
Monoisotopic Mass331.11366728 g/mol
Topological Polar Surface Area140 Ų
Heavy Atom Count21
Formal Charge0
Complexity349
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count1
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 6  
Drug NameAxid
PubMed HealthNizatidine (By mouth)
Drug ClassesAntiulcer, Gastric Acid Secretion Inhibitor
Drug LabelNizatidine (USP) is a histamine H2-receptor antagonist. Chemically, it is N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine. The structural formula is as follows: Nizatidine has the empirical formula
Active IngredientNizatidine
Dosage FormSolution
RouteOral
Strength15mg/ml
Market StatusPrescription
CompanyBraintree

2 of 6  
Drug NameAxid ar
Active IngredientNizatidine
Dosage FormTablet
RouteOral
Strength75mg
Market StatusOver the Counter
CompanyPfizer

3 of 6  
Drug NameNizatidine
PubMed HealthNizatidine (By mouth)
Drug ClassesAntiulcer, Gastric Acid Secretion Inhibitor
Drug LabelNizatidine USP is a histamine H2-receptor antagonist. Chemically, it is N-[2-[[[2-[(Dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine. The structural formula is represented below:C12H21N5O2S2...
Active IngredientNizatidine
Dosage FormCapsule; Solution
RouteOral
Strength150mg; 300mg; 15mg/ml
Market StatusPrescription
CompanyAmneal Pharms; Mylan Pharms; Ani Pharms; Sandoz; Watson Labs; Glenmark Generics; Dr Reddys Labs

4 of 6  
Drug NameAxid
PubMed HealthNizatidine (By mouth)
Drug ClassesAntiulcer, Gastric Acid Secretion Inhibitor
Drug LabelNizatidine (USP) is a histamine H2-receptor antagonist. Chemically, it is N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine. The structural formula is as follows: Nizatidine has the empirical formula
Active IngredientNizatidine
Dosage FormSolution
RouteOral
Strength15mg/ml
Market StatusPrescription
CompanyBraintree

5 of 6  
Drug NameAxid ar
Active IngredientNizatidine
Dosage FormTablet
RouteOral
Strength75mg
Market StatusOver the Counter
CompanyPfizer

6 of 6  
Drug NameNizatidine
PubMed HealthNizatidine (By mouth)
Drug ClassesAntiulcer, Gastric Acid Secretion Inhibitor
Drug LabelNizatidine USP is a histamine H2-receptor antagonist. Chemically, it is N-[2-[[[2-[(Dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine. The structural formula is represented below:C12H21N5O2S2...
Active IngredientNizatidine
Dosage FormCapsule; Solution
RouteOral
Strength150mg; 300mg; 15mg/ml
Market StatusPrescription
CompanyAmneal Pharms; Mylan Pharms; Ani Pharms; Sandoz; Watson Labs; Glenmark Generics; Dr Reddys Labs

4.2 Therapeutic Uses

Anti-Ulcer Agents; Histamine H2 Antagonists

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


In the Zollinger-Ellison syndrome and other acid peptic disorders, the efficacy of nizatidine would be expected to be similar to that of ranitidine, but confirmation in clinical studies is required. Nizatidine relieves symptoms and heals lesions in patients with mild to moderate reflux esophagitis.

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 903


Histamine H2-receptor antagonists are indicated in the short-term treatment of active duodenal ulcer. They are also indicated (at reduced dosage) in the prevention of duodenal ulcer recurrence in selected patients. /Histamine H2-receptor antagonists; Included in US product labeling/

USP Convention. USPDI - Drug Information for the Health Care Professional. 16th ed. Volume I. Rockville, MD: U.S. Pharmaceutical Convention, Inc. 1996 (Plus updates)., p. 1611


Nizatidine ... /is/ indicated in the short-term treatment of active benign gastric ulcer. /Included in US product labeling/

USP Convention. USPDI - Drug Information for the Health Care Professional. 16th ed. Volume I. Rockville, MD: U.S. Pharmaceutical Convention, Inc. 1996 (Plus updates)., p. 1611


For more Therapeutic Uses (Complete) data for NIZATIDINE (8 total), please visit the HSDB record page.


4.3 Drug Warning

Nizatidine should be used with caution and the dose and/or frequency of administration reduced in patients with renal impairment (ie., creatinine clearance less than 50 ml/min), since the drug is excreted principally by the kidneys.

McEvoy G.K. (ed.). American Hospital Formulary Service-Drug Information 96. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1996 (Plus Supplements)., p. 2174


Symptomatic response to nizatidine should not be interpreted as precluding the presence of gastric malignancy.

McEvoy G.K. (ed.). American Hospital Formulary Service-Drug Information 96. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1996 (Plus Supplements)., p. 2174


Rhinitis, pharyngitis, sinusitis, or increased cough has occurred in about 2-10% of patients receiving nizatidine. Diaphoresis occurred more often with nizatidine therapy than with placebo but was not considered drug related because of its association with other concurrent adverse events (e.g., fever, anxiety). Pain, including back or chest pain, has been reported in approximately 2-4% of patients receiving nizatidine. Other adverse events reported in patients receiving nizatidine include myalgia, fever, infection, amblyopia, hyperuricemia, and impotence. In most studies, the incidence of these adverse effects, and of surgical procedures or accidental injuries, was similar in patients receiving nizatidine or placebo. Asymptomatic ventricular tachycardia, decreased libido, and gynecomastia have been reported rarely.

McEvoy G.K. (ed.). American Hospital Formulary Service-Drug Information 96. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1996 (Plus Supplements)., p. 2174


Urticaria occurred more often with nizatidine therapy (0.5% of patients) than with placebo (0.1% of patients) in placebo-controlled clinical studies. Rash, pruritus, or exfoliative dermatitis has occurred in up to 2% of patients receiving nizatidine. Serum sickness-like reactions, anaphylaxis, bronchospasm, laryngeal edema, eosinophilia, vasculitis, and erythema multiforme also have been reported rarely.

McEvoy G.K. (ed.). American Hospital Formulary Service-Drug Information 96. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1996 (Plus Supplements)., p. 2174


For more Drug Warnings (Complete) data for NIZATIDINE (7 total), please visit the HSDB record page.


4.4 Drug Indication

For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, active benign gastric ulcer, and active duodenal ulcer.


FDA Label


5 Pharmacology and Biochemistry
5.1 Pharmacology

Nizatidine is a competitive, reversible inhibitor of histamine at the histamine H2-receptors, particularly those in the gastric parietal cells. By inhibiting the action of histamine on stomach cells, nizatidine reduces stomach acid production. Nizatidine had no demonstrable antiandrogenic action. Full-dose therapy for the problems treated by nizatidine lasts no longer than 8 weeks. It has been demonstrated that treatment with a reduced dose of nizatidine is effective as maintenance therapy following healing of active duodenal ulcers.


5.2 MeSH Pharmacological Classification

Histamine H2 Antagonists

Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood. (See all compounds classified as Histamine H2 Antagonists.)


Anti-Ulcer Agents

Various agents with different action mechanisms used to treat or ameliorate PEPTIC ULCER or irritation of the gastrointestinal tract. This has included ANTIBIOTICS to treat HELICOBACTER INFECTIONS; HISTAMINE H2 ANTAGONISTS to reduce GASTRIC ACID secretion; and ANTACIDS for symptomatic relief. (See all compounds classified as Anti-Ulcer Agents.)


5.3 FDA Pharmacological Classification
5.3.1 Pharmacological Classes
Histamine-2 Receptor Antagonist [EPC]; Histamine H2 Receptor Antagonists [MoA]
5.4 ATC Code

A - Alimentary tract and metabolism

A02 - Drugs for acid related disorders

A02B - Drugs for peptic ulcer and gastro-oesophageal reflux disease (gord)

A02BA - H2-receptor antagonists

A02BA04 - Nizatidine


5.5 Absorption, Distribution and Excretion

Absorption

Rapid (bioavailability of nizatidine exceeds 70%)


Volume of Distribution

0.8 to 1.5 L/kg


Clearance

40-60 L/h

7 14 L/h [functionally anephric patients]


Nizatidine has a duration of action of up to 10 hours. It is eliminated primarily by the kidneys; 90% of the administered dose (65% as unchanged drug) is recovered in the urine within 16 hours.

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 904


Distribution of nizatidine into human body tissues and fluids has not been fully characterized. The apparent volume of distribution of the drug is reported to be 0.8-1.5 l/kg in adults and does not appear to be altered substantially in patients with renal dysfunction.

McEvoy G.K. (ed.). American Hospital Formulary Service-Drug Information 96. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1996 (Plus Supplements)., p. 2172


In one study, the oral bioavailability of nizatidine exceeded 70% and was not affected by food or the anticholinergic drug, propantheline. Its apparent volume of distribution is 1.2 l/kg. Systemic clearance (10 ml/min/kg) is decreased in uremic patients and in the elderly.

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 904


The safety and disposition of single oral doses of nizatidine were investigated in 8 young volunteers (aged 25-48 yr) who received 100-350 mg nizatidine and in 12 elderly volunteers (aged 66-79 yr) who received 100-300 mg. The nizatidine AUC was directly proportional to dose for both groups of volunteers. Calculated pharmacokinetic variables in the elderly versus the young were Tl/2 (1.9 versus 1.6 hr), apparent plasma clearance (32 versus 40 l/h) and apparent volume of distribution (1.2 versus 1.3 l/kg). The impaired renal function of some elderly volunteers prolonged nizatidine elimination and lowered its clearance. Renal impairment rather than advanced age per se was the predominant factor in decreasing the nizatidine elimination rate. No serious adverse effects occurred.

PMID:2888796 Callaghan JT et al; J Clin Pharmacol 27 (Aug): 618-24 (1987)


For more Absorption, Distribution and Excretion (Complete) data for NIZATIDINE (7 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

Hepatic. Less than 7% of an oral dose is metabolized as N2-monodes-methylnizatidine, an H2-receptor antagonist, which is the principal metabolite excreted in the urine. Other likely metabolites are the N2-oxide (less than 5% of the dose) and the S-oxide (less than 6% of the dose).


Nizatidine is metabolized in the liver to N-desmethylnizatidine, nizatidine N-oxide, and nizatidine sulfoxide. Of these metabolites, only N-desmethylnizatidine has histamine H2-receptor blocking activity; studies in animals indicate that this metabolite is approximately 60% as active as nizatidine in blocking gastric acid secretion. Orally administered nizatidine undergoes minimal metabolism on first pass through the liver.

McEvoy G.K. (ed.). American Hospital Formulary Service-Drug Information 96. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1996 (Plus Supplements)., p. 2172


5.7 Biological Half-Life

1-2 hours


Half life is 10 hours.

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 904


5.8 Mechanism of Action

Nizatidine competes with histamine for binding at the H2-receptors on the gastric basolateral membrane of parietal cells. Competitive inhibition results in reduction of basal and nocturnal gastric acid secretions. The drug also decreases the gastric acid response to stimuli such as food, caffeine, insulin, betazole, or pentagastrin.


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