metoclopramide

Metoclopramide is a dopamine D2 antagonist that is used as an antiemetic.IC50 Value:Target: D2 ReceptorMetoclopramide is a dopamine receptor antagonist which has been used for treatment of a variety of gastrointestinal symptoms over the last thirty years. In various countries, metoclopramide is the antiemetic drug of choice in pregnant women. Findings provide reassurance regarding the safety of metoclopramide for the fetus when the drug is given to women to relieve nausea and vomiting during pregnancy. Evidence also supports its use for gastroparesis (poor stomach emptying) and gastroesophageal reflux disease. It appears to bind to dopamine D2 receptors where it is a receptor antagonist, and is also a mixed 5-HT3 receptor antagonist/ 5-HT4 receptor agonist.

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Endocrinology

[1]. Navari RM, Nagy CK, Gray SE. The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. Support Care Cancer. 2013 Jan 12.

[2]. Gutiérrez-Hermosillo H, Díaz de León-González E, Beltrán Santiago D et al. Metoclopramide as a risk factor for postprandial hyperglycemia in type 2 diabetes. Nutr Hosp. 2012 Jul-Aug;27(4):1267-71.

[3]. Ilan Matok, Sc.Pharm., Rafael Gorodischer, et al. The Safety of Metoclopramide Use in the First Trimester of Pregnancy. N Engl J Med 2009; 360:2528-2535.

[4]. DN Bateman, C Kahn, K Mashiter, DS Davies. Pharmacokinetic and concentration-effect studies with intravenous metoclopramide. British Journal of Clinical Pharmacology.1978,6(5): 401-407

CB-154 mesylate | SCH 23390 hydrochloride | Levodopa | Cabergoline | Thioridazine hydrochloride | Brexpiprazole | Domperidone | Trifluoperazine dihydrochloride | pimozide | Risperidone | SKF38393 HCl | Cariprazine | SERTINDOLE | Fluphenazine (dihydrochloride) | Nomifensine

MOLECULAR FORMULA :

C14-H22-Cl-N3-O2

MOLECULAR WEIGHT :

299.84

WISWESSER LINE NOTATION :

2N2&2MVR DZ CG FO1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

632 mg/kg/59D-I

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - toxic psychosis Behavioral - excitement

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

3600 ug/kg/6D-I

TOXIC EFFECTS :

Behavioral - tremor Gastrointestinal - changes in structure or function of salivary glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

900 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - diplopia Behavioral - muscle contraction or spasticity

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

111 mg/kg/37W-I

TOXIC EFFECTS :

Peripheral Nerve and Sensation - fasciculations

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

2 mg/kg/1D-C

TOXIC EFFECTS :

Behavioral - excitement

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

2400 ug/kg

TOXIC EFFECTS :

Vascular - BP elevation not characterized in autonomic section

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

14 ug/kg

TOXIC EFFECTS :

Vascular - BP elevation not characterized in autonomic section Biochemical - Neurotransmitters or modulators (putative) - catecholamine levels in sympathetic nerves

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

750 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

114 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

340 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

270 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

96 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

190 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

33 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

600 mg/kg/30D-I

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in ovarian weight Related to Chronic Data - changes in uterine weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

34 mg/kg

SEX/DURATION :

male 60 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - impotence

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1155 mg/kg

SEX/DURATION :

female 33 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders

MUTATION DATA

TYPE OF TEST :

DNA damage

TEST SYSTEM :

Human Leukocyte

DOSE/DURATION :

100 nmol/L

REFERENCE :

CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 12,1613,1991 *** REVIEWS *** TOXICOLOGY REVIEW AJHPA9 American Journal of Hospital Pharmacy. (American Soc. of Hospital Pharmacists, 4630 Montgomery Ave., Bethesda, MD 20814) V.15- 1958- Volume(issue)/page/year: 38,829,1981 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5297 No. of Facilities: 20 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 821 (estimated) No. of Female Employees: 456 (estimated)