| Identification | Back Directory | [Name]
METOCLOPRAMIDE HCL | [CAS]
7232-21-5 | [Synonyms]
Eucil
reglan
cerucal
maxolon
EMperal
Maxeran
Gastrese
MetaMide
paspertin
Gastrobid
Gastrosil
GastroteM
Meclopran
DraclaMid
AKOS 92099
AHR-3070-C
CloproMate
primperan(tablet)
METOCLOPRAMIDE HCL
LABOTEST-BB LT00772087
Metoclopramide hydrochloride
METOCLOPRAMIDE HCL USP/EP/BP
METOCLOPRAMIDE MONOHYDROCHLORIDE
Metoclopramide hydrochloride ,99%
METOCLOPRAMIDEHYDROCHLORIDE,ANHYDROUS
METOCLOPRAMIDE HYDROCHLORIDE 5-HT3 SEROT ONIN ANTAG
Metoclopramide hydrochloride Solution in Water, 100μg/mL
2-Methoxy-4-amino-5-chloro-N,N-dimethylaminoethyl)benzamide
4-amino-5-chloro-n-(2-(diethylamino)ethyl)-o-anisamidehydrochloride
4-amino-5-chloro-n-(2-(diethylamino)ethyl)-o-anisamidmonohydrochloride
4-amino-5-chloro-N-(2-(diethylamino)ethyl)-o-anisamide monohydrochloride
4-amino-5-chloro-n-(2-(diethylamino)ethyl)-2-methoxy-benzamidmonohydroch
4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide monohydrochloride
Benzamide, 4-amino-5-chloro-N-2-(diethylamino)ethyl-2-methoxy-, monohydrochloride | [EINECS(EC#)]
206-662-9 | [Molecular Formula]
C14H23Cl2N3O2 | [MDL Number]
MFCD00058011 | [MOL File]
7232-21-5.mol | [Molecular Weight]
336.26 |
| Hazard Information | Back Directory | [Description]
Metoclopramide is an orally bioavailable serotonin (5-HT) receptor 5-HT3 antagonist with Ki and IC50 values of 995 and 308 nM, respectively, in rat cortical membranes.1,2 It is also a dopamine D2 receptor antagonist (IC50 = 483 nM in rat brain synaptic membranes).2 Oral administration of metoclopramide inhibits emesis induced by cisplatin (Item No. 13119) and apomorphine (Item No. 16094) in ferrets and dogs with ED50 values of 6.17 and 0.45 mg/kg, respectively.1,2 Metoclopramide reversibly inhibits human acetylcholinesterase (AChE) isolated from the caudate nucleus (Kis = 9.3 and 82 μM for competitive and non-competitive inhibition, respectively).3 Formulations containing metoclopramide have been used as anti-emetic and antipsychotic agents.4,5 | [Chemical Properties]
White Solid | [Originator]
Primperan,Delagrange,France,1964 | [Uses]
A D2DR inhibitor and an HTR3E inhibitor | [Uses]
Antiemetic;5-HT3 antagonist | [Uses]
Dopamine D2 receptor antagonist. Antiemetic. | [Manufacturing Process]
The N-(diethylaminoethyl)-2-methoxy-4-aminobenzamide used as the starting
material may be prepared from o-toluidine. The o-toluidine is initially nitrated
with nitric acid to produce 4-nitro-o-toluidine. The 4-nitro-o-toluidine is then
converted to 2-hydroxy-4-nitrotoluene by heating with nitrous acid. By
reacting the resulting 2-hydroxy-4-nitrotoluene with dimethyl sulfate, 2-
methoxy-4-nitrotoluene is formed. The 2-methoxy-4-nitrotoluene is oxidized
with potassium permanganate to produce 2-methoxy-4-nitrobenzoic acid. The
latter substituted benzoic acid is treated with thionyl chloride to form 2-
methoxy-4-nitrobenzoyl chloride. A methyl ethyl ketone solution of the 2-
methoxy-4-nitrobenzoyl chloride is added over a period of about 1? hours to
a methyl ethyl ketone solution containing an equal molecular quantity of N,Ndiethylethylene diamine while stirring and maintaining the temperature
between 0°C and 5°C. The N-(diethylaminoethyl)-2-methoxy-4-
nitrobenzamide hydrochloride formed precipitates. It is filtered, washed twice
with methyl ethyl ketone, dissolved in alcohol, and reduced catalytically in an
absolute isopropyl alcohol solution to form N-(diethylaminoethyl)-2-methoxy-
4-aminobenzamide. The base is obtained by precipitating with sodium
hydroxide.
80 g (0.3mol) of N-(2-diethylaminoethyl)-2-methoxy-4-aminobenzamide are
dissolved in small portions in 150 cc of acetic acid. The mixture is cooled and
45 g (0.45 mol) of acetic anhydride are added, and the solution obtained is
heated for two hours on a water bath. After cooling, the solution is decanted
into a round-bottomed flask with a stirrer, a thermometer and a tube for
introducing the chlorine. It is stirred and the current of chlorine is passed
through, the temperature being maintained between 20°C and 25°C. The
stirring is continued for one hour after the completion of the absorption of the
chlorine.
The mixture obtained is poured into 2 liters of water and the base is
precipitated with 30% soda. The precipitated base is extracted with 400 cc of
methylene chloride. After evaporation of the solvent, the N-(2-
diethylaminoethyl)-2-methoxy-4-acetamino-5-chlorobenzamide formed
crystallizes. The melting point is 86°C to 87°C and the yield is 95%.
To obtain the corresponding amino derivative, 109 g of base are heated under
agitation in a round-bottomed flask with 300 cc of 35-36% concentrated
hydrochloric acid and 600 cc of water. It is heated on a water bath until
dissolution is complete, then maintained at boiling point for 90 minutes,
cooled, diluted with 1 liter of water, and neutralized with about 350 cc of 30%
soda. The N-(2-diethylaminoethyl)-2-methoxy-4-amino-5-chlorobenzamide
formed crystallizes, is centrifuged and washed in water. Its melting point is
122°C and the yield is 74%.
To obtain the corresponding dihydrochloride, the base is dissolved in absolute
alcohol (3 volumes) and to that solution is added 5 N alcoholic hydrochloric
acid. The dihydrochloride precipitates, is centrifuged and washed with alcohol.
It is a solid white material, having a melting point of 134°C to 135°C. | [Therapeutic Function]
Antiemetic | [Biochem/physiol Actions]
D2 antagonist; 5-HT3 antagonist; antipsychotic; anti-emetic. | [Clinical Use]
Nausea and vomiting | [Veterinary Drugs and Treatments]
Metoclopramide has been used in veterinary species for both its
GI stimulatory and antiemetic properties. It has been used clinically
for gastric stasis disorders, gastroesophageal reflux,
to allow
intubation of the small intestine, as a general antiemetic (for parvovirus,
uremic gastritis, etc.), and an antiemetic to prevent or treat
chemotherapy-induced vomiting. | [Drug interactions]
Potentially hazardous interactions with other drugs
Ciclosporin: increased ciclosporin blood levels. | [Metabolism]
Metoclopramide undergoes first-pass hepatic metabolism.
It is excreted in the urine, about 85% of a dose
being eliminated in 72 hours, 20% as unchanged
metoclopramide and the remainder as sulfate or
glucuronide conjugates, or as metabolites. About 5% of a
dose is excreted in faeces via the bile. |
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