Alaproclate (developmental code name GEA-654) is a drug that was being developed as an antidepressant by the

Swedish Swedish or ' may refer to: Anything from or related to Sweden, a country in Northern Europe. Or, specifically: * Swedish language, a North Germanic language spoken primarily in Sweden and Finland ** Swedish alphabet, the official alphabet used by ...

pharmaceutical company The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate sympto ...

Astra AB (now

AstraZeneca AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includi ...

) in the 1970s. It acts as a

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

(SSRI), and along with

zimelidine Zimelidine (INN, BAN) (brand names Zimeldine, Normud, Zelmid) was one of the first selective serotonin reuptake inhibitor (SSRI) antidepressants to be marketed. It is a pyridylallylamine, and is structurally different from other antidepressants ...

and

indalpine Indalpine (INN, BAN; brand name Upstène; developmental code name LM-5008) is a selective serotonin reuptake inhibitor (SSRI) class drug that was briefly marketed. It was discovered in 1977 by the pharmacologists Le Fur and Uzan at Pharmuka, a s ...

, was one of the first of its kind. Development was discontinued due to the observation of liver complications in rodent studies. In addition to its SSRI properties, alaproclate has been found to act as a non-competitive

NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

, but does not have discriminative stimulus properties similar to

phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted percept ...

Synthesis

Method for Treatment of Senile Dementia:Ulf H. A. Lindberg, Sven-Ove gren, (1984 to Astra Lakemedel Aktiebolag). Alaproclate-synthesis

The

Grignard reaction The Grignard reaction () is an organometallic chemical reaction in which alkyl, allyl, vinyl, or aryl-magnesium halides (Grignard reagent) is added to a carbonyl group in an aldehyde or ketone. This reaction is important for the formation of ...

between methyl 4-chlorophenylacetate 2449-43-1(1) with

methylmagnesium iodide Methylmagnesium chloride is an organometallic compound with the general formula CH3MgCl. This highly flammable, colorless, and moisture sensitive material is the simplest Grignard reagent and is commercially available, usually as a solution in tet ...

gives 1-(4-chlorophenyl)-2-methyl-2-propanol 468-97-3(2). Acylation with 2-bromopropionyl bromide 63-76-8(3) gives -(4-Chlorophenyl)-2-methylpropan-2-yl2-bromopropanoate
CID:13695101
(3). Displacement of halogen with ammonia leads to alaproclate (4).

References

Antidepressants Chloroarenes Propionate esters NMDA receptor antagonists Selective serotonin reuptake inhibitors Abandoned drugs {{nervous-system-drug-stub

Synthesis

See also

References