IFENPRODIL HEMITARTRATE Property

Melting point:

178-180°C

storage temp. 

Inert atmosphere,2-8°C

solubility 

DMSO (Slightly), Methanol (Slightly), Water (Slightly)

form 

White solid

color 

White

Water Solubility 

Soluble in water (15mM, gentle warming)

Stability:

Hygroscopic

Safety

Hazard Codes 

Xn

Risk Statements 

20/21/22-36/37/38

Safety Statements 

22-26-36-36/37

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H312Harmful in contact with skin

H315Causes skin irritation

H319Causes serious eye irritation

H332Harmful if inhaled

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

IFENPRODIL HEMITARTRATE Chemical Properties,Usage,Production

Chemical Properties

Crystalline Solid

Originator

Vadilex,Carriere,France,1972

Uses

Vasodilator (cerebral and peripheral)

Uses

Vasodilatator;Adrenergic antagonist

Uses

Ifenprodil (+)-tartrate salt has been used:

• to test the action in a KCl-induced cortical spreading depression (CSD) animal
• to study its effects on electrophysiological properties and spontaneous spikes in neocortical pyramidal cells
• to investigate its therapeutic effects

Definition

ChEBI: Ifenprodil tartrate is a member of piperidines.

Manufacturing Process

The initial steps involve reacting benzyl chloride with 4- hydroxypropiophenone. The benzyloxypropiophene thus obtained is first brominated and then reacted with 4-benzylpiperidine to give 1-(pbenzyloxyphenyl)-2-(4-benzyl-piperidino)propan-1-one.
The neutral tartrate may be prepared directly by reduction of 1-(pbenzyloxyphenyl)-2-(4-benzyl-piperidino)propan-1-one. For the reduction, a mixture of 175 g of ketone (0.425 mol) and 32 g of tartaric acid (0.213 mol) is hydrogenated at 50°C under pressure of 50 kg/cm2 in 440 ml of methanol in the presence of 12 g of palladium on charcoal.
The catalyst is filtered off at elevated temperature, and the filtrate is concentrated by evaporation under reduced pressure to a volume of 300 ml and added in a thin stream to 2.5 liters of diethyl ether with mechanical agitation. The precipitate is separated, washed with diethyl ether and dried in vacuo at 80° to 85°C for several hours. 325 g (96% yield) of the neutral tartrate of 1-(p-hydroxyphenyl)-2-(4-benzyl-piperidino)propan-1-ol are obtained.

Therapeutic Function

Vasodilator

General Description

Ifenprodil is a phenylethanolamine, which stimulates blood circulation. It has anticonvulsant and antinociceptive properties. Ifenprodil is used to treat posttraumatic stress disorder, cerebrovascular diseases and peripheral arterial obliterative disease. It blocks G protein-coupled inwardly-rectifying potassium channels (GIRKs) and interacts with α1 adrenergic, N-methyl-D-aspartate and serotonin receptors.

Biological Activity

Ifenprodil hemitartrate is a NMDA receptor antagonist, acting at the polyamine site. Also an α-adrenergic vasodilator. σ2 ligand displaying about 3-fold selectivity over σ1 sites.

Biochem/physiol Actions

NMDA antagonist acting at the polyamine site; neuroprotective agent; α-adrenergic central and peripheral vasodilator; α2 adrenergic receptor ligand.

in vitro

Ifenprodil treatment of oocytes, at NR1A/NR2B and NR1A/NR2A receptors, inhibited NMDA-induced currents with IC50 of 0.34 μM and 146 μM, respectively, and voltage-clamped at -70 mV. Ifenprodil acts as a weak open channel blocker of NR1A/NR2A receptors, the degree of inhibition of NR1A/NR2A receptors by 100 μM fenprodil is not affected by extracellular glycine concentration. Increasing glycine concentration decreased the inhibitory effect of 1mMIfenprodil on NR1A/NR2B receptors. Ifenprodil (10 μM) acts on young rat cortical neurons, a single population of receptors with high affinity for glycine, inhibits almost all NMDA receptor-evoked currents. Ifenprodil (10 μM) inhibited a significant proportion of high- and low-affinity components in aged rat cortical neurons, revealing three pharmacologically distinct distribution populations of NMDA receptors in a single neuron. Ifenprodil antagonizes NMDA receptors in an activity-dependent manner and also enhances the receptor's affinity for glutamate recognition site agonists. In the inhibition curves of Ifenprodil on 10μM and 100μM NMDA-evoked currents, IC50 was 0.88μM and 0.17μM, respectively. Ifenprodil (3μM) can enhance the control level of cultured rat cortical neurons. Enhanced by about 200%. Ifenprodil has a 39- and 50-fold enhanced affinity for NMDA receptors in the agonist-bound activated and desensitized states compared to the resting, agonist-unbound state. Ifenprodil binds to NMDA receptors with a 6-fold increased affinity for glutamate receptor agonists.

storage

Room temperature