(R)-1-Aminoindan

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(R)-1-Aminoindan
1-R-aminoindane.svg
Clinical data
Other names(R)-1-Aminoindane; (R)-(–)-1-Aminoindan; (R)-AI; (R)-1-AI; TVP-136; TV-136; (R)-(−)-1-Indanamine
Identifiers
  • (1R)-2,3-dihydro-1H-inden-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C9H11N
Molar mass 133.194 g·mol−1
3D model (JSmol)
  • C1CC2=CC=CC=C2[C@@H]1N
  • InChI=1S/C9H11N/c10-9-6-5-7-3-1-2-4-8(7)9/h1-4,9H,5-6,10H2/t9-/m1/s1
  • Key:XJEVHMGJSYVQBQ-SECBINFHSA-N

(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). [1] In contrast to rasagiline, it lacks significant monoamine oxidase inhibition. [2] [3] In addition, unlike selegiline and its amphetamine metabolites, it lacks monoamine reuptake-inhibiting and -releasing activities and associated amphetamine-like psychostimulant effects. [2] [3] [4] However, (R)-1-aminoindan retains neuroprotective effects and certain other activities. [2] [3] [4] [5] [6]

Contents

Pharmacology

Pharmacodynamics

In contrast to rasagiline, (R)-1-aminoindan is either devoid of monoamine oxidase inhibition or shows only weak inhibition of MAO-B. [2] [3] Unlike selegiline and its levomethamphetamine and levoamphetamine metabolites, rasagiline and (R)-1-aminoindan have no amphetamine-like activity. [2] [3] [4]

In spite of the preceding however, (R)-1-aminoindan is not lacking in pharmacological activity. [2] [3] Like rasagiline, it shows neuroprotective activity in some experimental models. [2] [3] In addition, (R)-1-aminoindan has been found to enhance striatal dopaminergic neurotransmission and to improve motor function independent of MAO inhibition in animal models of Parkinson's disease. [3]

2-Aminoindan, a closely related positional isomer of 1-aminoindan, is known to inhibit the reuptake and induce the release of dopamine and norepinephrine and to produce psychostimulant-like effects in rodents, albeit with lower potency than amphetamine. [1] [5] However, rasagiline does not metabolize into this compound, and 1-aminoindan does not have the same effects. [1] [5] 1-Aminoindan has been found to inhibit the reuptake of norepinephrine 28-fold less potently than 2-aminoindan and to inhibit the reuptake of dopamine 300-fold less potently than 2-aminoindan, with IC50 Tooltip half maximal inhibitory concentration values for dopamine reuptake inhibition in one study of 0.4 μM for amphetamine, 3.3 μM for 2-aminoindan, and 1 mM for 1-aminoindan. [5] [6] [7] In contrast to 2-aminoindan, which increased locomotor activity in rodents (+49%), 1-aminoindan suppressed locomotor activity (–69%). [5] On the other hand however, 1-aminoindan has been found to enhance the psychostimulant-like effects of amphetamine in rodents. [6]

Chemistry

(R)-1-Aminoindan is a 1-aminoindan derivative. [1] It is specifically the (R)-enantiomer of 1-aminoindan, which is a racemic mixture of (R)- and (S)-enantiomers. [8] 1-Aminoindan is structurally related to 2-aminoindan. [1] A number of derivatives of 1- and 2-aminoindan are known. [1]

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">Tranylcypromine</span> Irreversible non-selective MAO inhibitor Antidepressant drug

Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively. It is also effective in the treatment of ADHD.

<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 and used off-label 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

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<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.

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<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 (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">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of a monoamine neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs induce their effects in the body and/or brain via the release of monoamine neurotransmitters, e.g., trace amines, many substituted amphetamines, and related compounds.

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

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<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

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<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">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">SU-11739</span> Monoamine oxidase inhibitor

SU-11739 is an experimental monoamine oxidase inhibitor (MAOI) that was never marketed.

<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. 1 2 3 4 5 6 Pinterova N, Horsley RR, Palenicek T (2017). "Synthetic Aminoindanes: A Summary of Existing Knowledge". Frontiers in Psychiatry. 8: 236. doi: 10.3389/fpsyt.2017.00236 . PMC   5698283 . PMID   29204127. 2-AI selectively inhibited just NET, and for SERT and DAT it has low potency. Apart from inhibitory actions on transporter molecules, aminoindanes have been shown to cause transporter-mediated release (reverse transport) of monoamines: MDAI released 5-HT and NE, 5-IAI released 5-HT and DA, and 2-AI released NE and DA (33).
  2. 1 2 3 4 5 6 7 Chen JJ, Swope DM (August 2005). "Clinical pharmacology of rasagiline: a novel, second-generation propargylamine for the treatment of Parkinson disease". Journal of Clinical Pharmacology. 45 (8): 878–894. doi:10.1177/0091270005277935. PMID   16027398. S2CID   24350277. Archived from the original on 11 July 2012.
  3. 1 2 3 4 5 6 7 8 Müller T (October 2014). "Pharmacokinetic/pharmacodynamic evaluation of rasagiline mesylate for Parkinson's disease". Expert Opinion on Drug Metabolism & Toxicology. 10 (10): 1423–1432. doi:10.1517/17425255.2014.943182. PMID   25196265.
  4. 1 2 3 Schapira A, Bate G, Kirkpatrick P (August 2005). "Rasagiline". Nature Reviews. Drug Discovery. 4 (8): 625–626. doi:10.1038/nrd1803. PMID   16106586.
  5. 1 2 3 4 5 Brandt SD, Braithwaite RA, Evans-Brown M, Kicman AT (2013). "Aminoindane Analogues". Novel Psychoactive Substances. Elsevier. pp. 261–283. doi:10.1016/b978-0-12-415816-0.00011-0. ISBN   978-0-12-415816-0.
  6. 1 2 3 Speiser Z, Levy R, Cohen S (1998). "Effects of N-propargyl-1-(R)aminoindan (Rasagiline) in models of motor and cognition disorders". MAO — the Mother of all Amine Oxidases. Journal of Neural Transmission. Supplement. Vol. 52. pp. 287–300. doi:10.1007/978-3-7091-6499-0_29. ISBN   978-3-211-83037-6. PMID   9564629.
  7. ↑ Horn AS, Snyder SH (March 1972). "Steric requirements for catecholamine uptake by rat brain synaptosomes: studies with rigid analogs of amphetamine". The Journal of Pharmacology and Experimental Therapeutics. 180 (3): 523–530. PMID   5012779.
  8. ↑ "1-Aminoindan". PubChem. Retrieved 1 September 2024.
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