SU-11739

Last updated
SU-11739
SU-11739.svg
Clinical data
Other namesAGN-1133; J-508; N-Methyl-N-propargyl-1-aminoindane; (±)-N-Methylrasagiline; (RS)-N-Methylrasagiline
Identifiers
  • N-methyl-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C13H15N
Molar mass 185.270 g·mol−1
3D model (JSmol)
  • CN(CC#C)C1CCC2=CC=CC=C12
  • InChI=1S/C13H15N/c1-3-10-14(2)13-9-8-11-6-4-5-7-12(11)13/h1,4-7,13H,8-10H2,2H3
  • Key:CSVGVHNFFZWQJU-UHFFFAOYSA-N

SU-11739 (other developmental code names AGN-1133, J-508; also known as N-methyl-N-propargyl-1-aminoindane) [1] is an experimental monoamine oxidase inhibitor (MAOI) that was never marketed. [2] [3] [4] [5]

It is a dual or non-selective irreversible monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitor, with preference for inhibition of MAO-B over MAO-A. [3] [4] It is less selective for MAO-B inhibition than AGN-1135 (racemic rasagiline) or rasagiline. [3] In addition to its MAOI activity, SU-11739 has been reported to have strong activity as a catecholamine releasing agent. [6] Similarly to rasagiline, but unlike selegiline and desmethylselegiline, SU-11739 is not a monoaminergic activity enhancer (MAE). [5]

The drug is the racemic N-methylated analogue of rasagiline. [2] [3] [4] It is also a ring-cyclized analogue of pargyline with about 20 times the MAOI potency of pargyline. [7]

SU-11739 was discovered before rasagiline and was patented in 1965. [8]

Related Research Articles

<span class="mw-page-title-main">Monoamine oxidase inhibitor</span> Type of medication

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.

<span class="mw-page-title-main">Tyramine</span> Chemical compound

Tyramine, also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs).

<span class="mw-page-title-main">Selegiline</span> Monoamine oxidase inhibitor

Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl, Zelapar, and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It has also been studied for a variety of other indications, but has not been formally approved for any other use. The medication in the form licensed for depression has modest effectiveness for this condition that is similar to that of other antidepressants. Selegiline is provided as a swallowed tablet or capsule or an orally disintegrating tablet (ODT) for Parkinson's disease and as a patch applied to skin for depression.

<span class="mw-page-title-main">Deprenyl</span> Pharmaceutical drug

Deprenyl, also known by its developmental code name E-250 and as N-propargylmethamphetamine, is the racemic mixture of D-deprenyl and L-deprenyl (selegiline). It was discovered in 1961 in Hungary at Chinoin Pharmaceutical Company by Zoltan Ecseri and József Knoll, was patented in 1962, and was first described in the literature in 1964 or 1965.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.

<span class="mw-page-title-main">Rasagiline</span> Chemical compound

Rasagiline, sold under the brand name Azilect among others, is a medication which is used in the treatment of Parkinson's disease. It is used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases. The drug is taken by mouth.

<span class="mw-page-title-main">Pargyline</span> Chemical compound

Pargyline, sold under the brand name Eutonyl among others, is a monoamine oxidase inhibitor (MAOI) medication which has been used to treat hypertension but is no longer marketed. It has also been studied as an antidepressant, but was never licensed for use in the treatment of depression. The drug is taken by mouth.

<span class="mw-page-title-main">Benzofuranylpropylaminopentane</span> Chemical compound

(–)-Benzofuranylpropylaminopentane is an experimental drug related to selegiline which acts as a monoaminergic activity enhancer (MAE). It is orally active in animals.

<span class="mw-page-title-main">Phenylpropylaminopentane</span> Stimulant drug of the substituted phenethylamine class

1-Phenyl-2-propylaminopentane is an experimental drug related to selegiline which acts as a catecholaminergic activity enhancer (CAE).

<span class="mw-page-title-main">Monoamine oxidase B</span> Protein-coding gene in the species Homo sapiens

Monoamine oxidase B, also known as MAO-B, is an enzyme that in humans is encoded by the MAOB gene.

<span class="mw-page-title-main">Levoamphetamine</span> CNS stimulant and isomer of amphetamine

Levoamphetamine is a stimulant medication which is used in the treatment of certain medical conditions. It was previously marketed by itself under the brand name Cydril, but is now available only in combination with dextroamphetamine in varying ratios under brand names like Adderall and Evekeo. The drug is known to increase wakefulness and concentration in association with decreased appetite and fatigue. Pharmaceuticals that contain levoamphetamine are currently indicated and prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), obesity, and narcolepsy in some countries. Levoamphetamine is taken by mouth.

<span class="mw-page-title-main">Pheniprazine</span> Chemical compound

Pheniprazine, formerly sold under the brand names Catron and Cavodil, is an irreversible and non-selective monoamine oxidase inhibitor (MAOI) of the hydrazine group that was used as an antidepressant to treat depression in the 1960s. It was also used in the treatment of angina pectoris and schizophrenia. Pheniprazine has been largely discontinued due to toxicity concerns such as jaundice, amblyopia, and optic neuritis.

<span class="mw-page-title-main">Moussa B. H. Youdim</span> Israeli neuroscientist and pharmacologist

Moussa B. H. Youdim is an Israeli neuroscientist specializing in neurochemistry and neuropharmacology. He is the discoverer of both monoamine oxidase (MAO) B inhibitors l-deprenyl (Selegiline) and rasagiline (Azilect) as anti-Parkinson drugs which possess neuroprotective activities. He is currently professor emeritus at Technion - Faculty of Medicine and President of Youdim Pharmaceuticals.

<span class="mw-page-title-main">Monoaminergic activity enhancer</span> Class of compounds in the nervous system

Monoaminergic activity enhancers (MAE), also known as catecholaminergic/serotonergic activity enhancers (CAE/SAE), are a class of compounds that enhance the action potential-evoked release of monoamine neurotransmitters in the nervous system. MAEs are distinct from monoamine releasing agents (MRAs) like amphetamine and fenfluramine in that they do not induce the release of monoamines from synaptic vesicles but rather potentiate only nerve impulse propagation-mediated monoamine release. That is, MAEs increase the amounts of monoamine neurotransmitters released by neurons per electrical impulse.

<span class="mw-page-title-main">Desmethylselegiline</span> Chemical compound

Desmethylselegiline (DMS), also known as norselegiline or as N-propargyl-L-amphetamine, is an active metabolite of selegiline, a medication used in the treatment of Parkinson's disease and depression.

<span class="mw-page-title-main">Pharmacology of selegiline</span> Pharmacology of the antiparkinsonian and antidepressant selegiline

The pharmacology of selegiline pertains to the pharmacodynamic and pharmacokinetic properties of the antiparkinsonian and antidepressant selegiline (L-deprenyl). Selegiline is available in a few different forms, including oral tablets and capsules, orally disintegrating tablets (ODTs), and transdermal patches. These forms have differing pharmacological properties.

<span class="mw-page-title-main">Indolylpropylaminopentane</span> A synthetic monoaminergic activity enhancer drug

Indolylpropylaminopentane (IPAP), also known as α,N-dipropyltryptamine (α,N-DPT), is a monoaminergic activity enhancer (MAE) that is closely related to benzofuranylpropylaminopentane (BPAP) and phenylpropylaminopentane (PPAP). It is a tryptamine derivative and the corresponding analogue of PPAP and BPAP with an indole ring instead of a benzene ring or benzofuran ring, respectively. MAEs are agents that enhance the action potential-mediated release of monoamine neurotransmitters.

<span class="mw-page-title-main">(R)-1-Aminoindan</span> Major metabolite of rasagiline

(R)-1-Aminoindan ((R)-1-AI; developmental code name TVP-136 or TV-136), or (R)-1-aminoindane, is the major metabolite of the selective MAO-B inhibitor and antiparkinsonian agent rasagiline ((R)-N-propargyl-1-aminoindan). In contrast to rasagiline, it lacks significant monoamine oxidase inhibition. In addition, unlike selegiline and its amphetamine metabolites, it lacks monoamine reuptake-inhibiting and -releasing activities and associated amphetamine-like psychostimulant effects. However, (R)-1-aminoindan retains neuroprotective effects and certain other activities.

<span class="mw-page-title-main">1-Aminoindane</span> Chemical compound

1-Aminoindane (1-AI), also known as 1-aminoindan, 1-indanylamine, or 1-indanamine, is an aminoindane. It is a positional isomer of 2-aminoindane. A variety of notable derivatives of 1- and 2-aminoindane are known. The (R)-enantiomer of 1-aminoindan, (R)-1-aminoindan, is pharmacologically active and is an active metabolite of the antiparkinsonian agent rasagiline.

<span class="mw-page-title-main">AGN-1135</span> A monoamine oxidase inhibitor and the racemic form of rasagiline

AGN-1135 is a monoamine oxidase inhibitor (MAOI) that was never marketed. It is the racemic form of rasagiline and is a mixture of the R(+)-enantiomer and S(–)-enantiomer (TVP-1022). Like rasagiline, AGN-1135 is a selective monoamine oxidase B (MAO-B) inhibitor. Virtually all of the MAOI activity of AGN-1135 lies in rasagiline, which is several orders of magnitude more potent as an MAO-B inhibitor than the S(–)-enantiomer. In relation to this, enantiopure rasagiline was developed and marketed for use as a pharmaceutical drug rather than AGP-1135.

References

  1. ↑ Tipton KF, Fowler CJ, McCrodden JM, Strolin Benedetti M (January 1983). "The enzyme-activated irreversible inhibition of type-B monoamine oxidase by 3-(4-[(3-chlorophenyl)methoxy]phenyl)-5-[(methylamino) methyl]-2-oxazolidinone methanesulphonate (compound MD 780236) and the enzyme-catalysed oxidation of this compound as competing reactions". Biochem J. 209 (1): 235–242. doi:10.1042/bj2090235. PMC   1154077 . PMID   6847610. Clorgyline hydrochloride was a gift from May and Baker, Dagenham, Essex, U.K. L-Deprenyl hydrochloride and compound J-508 [N-methyl-N-propargyl-L-aminoindane hydrochloride (compound AGN 1133; compound Su-11739)] were gifts from Professor J. Knoll, Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
  2. 1 2 Finberg JP (February 2020). "The discovery and development of rasagiline as a new anti-Parkinson medication". Journal of Neural Transmission. 127 (2): 125–130. doi:10.1007/s00702-020-02142-w. PMID   31974721.
  3. 1 2 3 4 Weinreb O, Amit T, Bar-Am O, Youdim MB (November 2010). "Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity". Progress in Neurobiology. 92 (3): 330–344. doi:10.1016/j.pneurobio.2010.06.008. PMID   20600573.
  4. 1 2 3 Youdim MB, Bakhle YS (January 2006). "Monoamine oxidase: isoforms and inhibitors in Parkinson's disease and depressive illness". British Journal of Pharmacology. 147 (Suppl 1): S287–S296. doi:10.1038/sj.bjp.0706464. PMC   1760741 . PMID   16402116.
  5. 1 2 Miklya I (June 2014). "Essential difference between the pharmacological spectrum of (-)-deprenyl and rasagiline". Pharmacol Rep. 66 (3): 453–458. doi:10.1016/j.pharep.2013.11.003. PMID   24905523.
  6. ↑ Miklya I (March 2008). "(-)-deprenil, az N-metilprogargilamin-1-aminoindan (J-508) és a J-508 dezmetil analógjának (rasagilin) összehasonlító farmakológiai analízise" [A comparison of the pharmacology of (-)-deprenyl to N-methylpropargylamine-1-aminoindane (J-508) and rasagiline, the desmethyl-analogue of J-508](PDF). Neuropsychopharmacol Hung (in Hungarian). 10 (1): 15–22. PMID   18771016.
  7. ↑ Huebner CF, Donoghue EM, Plummer AJ, Furness PA (November 1966). "N-methyl-n-2-propynyl-l-indanamine. A protent monoamine oxidase inhibitor". Journal of Medicinal Chemistry. 9 (6): 830–832. doi:10.1021/jm00324a009. PMID   5972038.
  8. ↑ US 3201470,Huebner CF,issued 17 August 1965, assigned to CIBA


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