(R)-1-Aminoindane

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(R)-1-Aminoindane
1-R-aminoindane.svg
Clinical data
Other names(R)-1-Aminoindan; (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-Aminoindane ((R)-1-AI; developmental code name TVP-136 or TV-136), or (R)-1-aminoindan, is the major metabolite of the selective MAO-B inhibitor and antiparkinsonian agent rasagiline ((R)-N-propargyl-1-aminoindane). [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-aminoindane retains neuroprotective effects and certain other activities. [2] [3] [4] [5] [6]

Contents

Pharmacology

Pharmacodynamics

In contrast to rasagiline, (R)-1-aminoindane 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-aminoindane have no amphetamine-like activity. [2] [3] [4]

In spite of the preceding however, (R)-1-aminoindane is not lacking in pharmacological activity. [2] [3] Like rasagiline, it shows neuroprotective activity in some experimental models. [2] [3] In addition, (R)-1-aminoindane 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-Aminoindane, a closely related positional isomer of 1-aminoindane, 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-aminoindane does not have the same effects. [1] [5] 1-Aminoindane has been found to inhibit the reuptake of norepinephrine 28-fold less potently than 2-aminoindane 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-aminoindane. [5] [6] [7] In contrast to 2-aminoindan, which increased locomotor activity in rodents (+49%), 1-aminoindane suppressed locomotor activity (–69%). [5] On the other hand however, 1-aminoindane has been found to enhance the psychostimulant-like effects of amphetamine in rodents. [6]

Chemistry

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

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. doi:10.1016/S0022-3565(25)29135-2. PMID   5012779.
  8. ↑ "1-Aminoindan". PubChem. Retrieved 1 September 2024.
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