4-Amino-5-chlor-N-[2-(diethylamino)ethyl]-2-methoxybenzamidmonohydrochlorid

Bezeichnung:4-Amino-5-chlor-N-[2-(diethylamino)ethyl]-2-methoxybenzamidmonohydrochlorid

CAS-Nr7232-21-5

Englisch Name:METOCLOPRAMIDE HCL

CBNumberCB4236007

SummenformelC14H23Cl2N3O2

Molgewicht336.26

MOL-Datei7232-21-5.mol

Synonyma

4-Amino-5-chlor-N-[2-(diethylamino)ethyl]-2-methoxybenzamidmonohydrochlorid

4-Amino-5-chlor-N-[2-(diethylamino)ethyl]-2-methoxybenzamidmonohydrochlorid physikalisch-chemischer Eigenschaften

Schmelzpunkt	171-173°C
storage temp.	2-8°C
Löslichkeit	H₂O: soluble
Aggregatzustand	solid
Farbe	white

Sicherheit

Kennzeichnung gefährlicher	Xn
R-Sätze:	22-36/37/38
S-Sätze:	26-36
WGK Germany	3
RTECS-Nr.	BZ3325000
HS Code	29242990

Gefahreninformationscode (GHS)

METOCLOPRAMIDE HCL Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Beschreibung
Metoclopramide is an orally bioavailable serotonin (5-HT) receptor 5-HT₃ antagonist with K_i and IC₅₀ values of 995 and 308 nM, respectively, in rat cortical membranes. It is also a dopamine D₂ receptor antagonist (IC₅₀ = 483 nM in rat brain synaptic membranes). Oral administration of metoclopramide inhibits emesis induced by cisplatin and apomorphine in ferrets and dogs with ED₅₀ values of 6.17 and 0.45 mg/kg, respectively. Metoclopramide reversibly inhibits human acetylcholinesterase (AChE) isolated from the caudate nucleus (K_is = 9.3 and 82 μM for competitive and non-competitive inhibition, respectively). Formulations containing metoclopramide have been used as anti-emetic and antipsychotic agents.
Chemische Eigenschaften
White Solid
Originator
Primperan,Delagrange,France,1964
Verwenden
A D2DR inhibitor and an HTR3E inhibitor
Verwenden
Antiemetic;5-HT3 antagonist
Verwenden
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.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Ciclosporin: increased ciclosporin blood levels.
Stoffwechsel
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.

METOCLOPRAMIDE HCL Upstream-Materialien And Downstream Produkte

4-Amino-5-chlor-N-[2-(diethylamino)ethyl]-2-methoxybenzamidmonohydrochlorid Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

7232-21-5, METOCLOPRAMIDE HCL Verwandte Suche:

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