Midodrine hydrochloride Chemical Properties

Melting point:

192-193°C

storage temp. 

-20°C Freezer

InChIKey

MGCQZNBCJBRZDT-UHFFFAOYSA-N

CAS DataBase Reference

3092-17-9(CAS DataBase Reference)

Safety Information

Hazard Codes 

T

Risk Statements 

25

Safety Statements 

45

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

RTECS 

AB4343000

HS Code 

29242990

MSDS

• Language:English Provider:SigmaAldrich

Midodrine hydrochloride Usage And Synthesis

Chemical Properties

Crystalline Solid

Originator

Gutron,Hormonchemie,W. Germany,1977

Uses

morphine antagonist

Uses

A phenylalkanolamine derivative which has been found to be effective in treating hypertensive conditions due to their long lasting blood pressure increasing effects

Definition

ChEBI: A hydrochloride resulting from the combination of equimolar amounts of midodrine and hydrogen chloride. Midodrine is a direct-acting sympathomimetic with selective alpha-adrenergic agonist activity. The hydrochloride salt is used as a periph ral vasoconstrictor in the treatment of certain hypotensive states. The main active moiety is its major metabolite, deglymidodrine.

Manufacturing Process

19.5 parts of carbobenzoxyglycine, 7.1 parts of triethylamine and 162 parts ofdry toluene are mixed with 11.2 parts of isovaleric acid chloride at 0°C toform the mixed anhydride and the mixture is agitated for two hours at 0°C.32.4 parts of 1-(2',5'-dimethoxyphenyl)-2-aminoethanol-(1) are then added,the mixture is agitated for four hours at a temperature between 0°C and+10°C and then left to stand overnight at that temperature. A thick crystalpaste forms. The reaction product is dissolved in 450 parts of ethyl acetateand 200 parts of water. The ethyl acetate solution is separated, washed withhydrochloric acid, sodium bicarbonate solution and water, dried over sodiumsulfate and inspissated. The inspissation residue is digested with 342 parts ofxylene, the required product crystallizing out. 34.9 parts of 1-(2',5'-dimethoxyphenyl)-2-(N-carbobenzoxyglycineamido)-ethanol-(1) are obtained.66.2 parts of 1-(2',5'-dimethoxyphenyl)-2-(N-carbobenzoxyglycineamido)-ethanol-(1) are hydrogenated in the presence of 6.6 parts of palladium carbon(10%) in 2,000 parts of glacial acetic acid. When no more hydrogen isabsorbed (3 mols of hydrogen are used), hydrogenation stops. The catalyst isremoved by suction and the equivalent quantity of hydrochloric acid in ethanolis added to the filtrate with agitation. During further agitation at roomtemperature 28.6 parts of crude 1-(2',5'-dimethoxyphenyl)-2-glycineamidoethanol-(1)hydrochloride crystallize, and are isolated andrecrystallized from water-methanol for purification. 22.1 parts of pure productare obtained with a melting point of 192°C to 193°C.
An alternative synthesis route is described by Kleeman and Engel.

brand name

Orvaten (UpsherSmith); Proamatine (Shire).

Therapeutic Function

Peripheral vasotonic, Antihypotensive

General Description

Midodrine is the N-glycyl prodrug ofthe selectiveα1-agonist desglymidodrine. Removal of theN-glycyl moiety from midodrine occurs readily in the liver aswell as throughout the body, presumably by amidases.Midodrine is orally active and represents another example ofa dimethoxy-β-phenylethylamine derivative that is used therapeuticallyfor its vasoconstrictor properties. Specifically, it isused in the treatment of symptomatic orthostatic hypotension.

Clinical Use

Treatment of orthostatic hypotension, including dialysis related hypotension

Drug interactions

Potentially hazardous interactions with other drugs
Adrenergic neurone blockers: midodrine antagonises hypotensive effect.
Anaesthetics: risk of arrhythmias if given with volatile anaesthetics.
Antidepressants: risk of arrhythmias and hypertension if given with tricyclic antidepressants, MAOIs and moclobemide.
Antihypertensives: antagonise hypertensive effect of midodrine; risk of severe hypertension if given with beta-blockers.
Dopaminergics: avoid with rasagiline and selegiline.
Other drugs which increase blood pressure: enhanced hypertensive effect.

Metabolism

Undergoes enzymatic hydrolysis in the systemic circulation to an active metabolite (desglymidodrine)

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