| Identification | More | [Name]
Metoclopramide hydrochloride | [CAS]
54143-57-6 | [Synonyms]
METOCLOPRAMIDE HYDROCHLORIDE, MONOHYDRATE
GastreseL.A
Gastrobidcontinus
METOCLOPRAMIDEHYDROCHLORIDE,MONOHYDRATE,USP
Gastromax
4-Amino-5-chloro-N-(2-diethylaminoethyl)-2-methoxybenzamide hydrochloride
Metoclopramide hydrochloride | [EINECS(EC#)]
641-713-2 | [Molecular Formula]
C14H25Cl2N3O3 | [MDL Number]
MFCD00150634 | [Molecular Weight]
354.27 | [MOL File]
54143-57-6.mol |
| Chemical Properties | Back Directory | [Melting point ]
182.5-184° | [storage temp. ]
Inert atmosphere,2-8°C | [solubility ]
Methanol (Slightly), Water (Slightly) | [form ]
neat | [color ]
White to Off-White | [Water Solubility ]
It is very soluble in water, easily soluble in ethyl alcohol, slightly soluble in dichloromethane. | [Sensitive ]
Light Sensitive | [Detection Methods]
T,NMR | [BCS Class]
3 | [InChIKey]
RVFUNJWWXKCWNS-UHFFFAOYSA-N | [CAS DataBase Reference]
54143-57-6(CAS DataBase Reference) |
| Hazard Information | Back Directory | [Originator]
Primperan,Delagrange,France,1964 | [Uses]
Dopamine receptor antagonist; antiemetic. | [Definition]
ChEBI: A hydrate that is the monohydrate form of metoclopramide monohydrochloride. | [Indications]
Metoclopramide (Reglan) stimulates upper GI tract
motility and has both central and peripheral actions.
Centrally, it is a dopamine antagonist, an action that is
important both for its often desirable antiemetic effect
and other less desirable effects. Peripherally, it stimulates
the release of intrinsic postganglionic stores of
acetylcholine and sensitizes the gastric smooth muscle
to muscarinic stimulation. The ability of metoclopramide
to antagonize the inhibitory neurotransmitter
effect of dopamine on the GI tract results in increased
gastric contraction and enhanced gastric emptying and
small bowel transit. | [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. | [Brand name]
Maxolon (King); Reglan (Baxter
Healthcare); Reglan (Robins); Reglan (Schwarz Pharma). | [Therapeutic Function]
Antiemetic | [General Description]
Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.
Metoclopramide Hydrochloride is an antiemetic drug and is generally used for the treatment of gastrointestinal disorders. It can also exhibit sedative, extrapyrimidal, and prolactin secretion stimulation actions. | [Mechanism of action]
Metoclopramide is rapidly absorbed following an
oral dose in a patient with intact gastric emptying. Peak
plasma concentration is achieved within 40 to 120 minutes.
With normal renal function, plasma half-life is
about 4 hours.About 20% of an oral dose is eliminated
unchanged in the urine, while 60% is eliminated as sulfate
or glucuronide conjugates. | [Clinical Use]
Improved gastric emptying will frequently alleviate
symptoms in patients with diabetic, postoperative, or idiopathic
gastroparesis. Since metoclopramide also can
decrease the acid reflux into the esophagus that results
from slowed gastric emptying or lower esophageal
sphincter pressure, the drug can be used as an adjunct in
the treatment of reflux esophagitis.
| [Side effects]
Side effects include fatigue, insomnia, and altered motor
coordination. Parkinsonian side effects and acute dystonic
reactions also have been reported. Metoclopramide
stimulates prolactin secretion, which can cause galactorrhea
and menstrual disorders. Extrapyramidal side effects
seen following administration of the phenothiazines,
thioxanthenes, and butyrophenones may be accentuated
by metoclopramide. | [storage]
Store at -20°C |
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