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(R)-1-Aminoindane

(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). 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-aminoindane retains neuroprotective effects and certain other activities.

Pharmacology

Pharmacodynamics

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

In spite of the preceding however, (R)-1-aminoindane is not lacking in pharmacological activity. Like rasagiline, it shows neuroprotective activity in some experimental models. 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.

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. However, rasagiline does not metabolize into this compound, and 1-aminoindane does not have the same effects. 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 values for dopamine reuptake inhibition in one study of 0.4μM for amphetamine, 3.3μM for 2-aminoindan, and 1mM for 1-aminoindane. In contrast to 2-aminoindan, which increased locomotor activity in rodents (+49%), 1-aminoindane suppressed locomotor activity (–69%). On the other hand however, 1-aminoindane has been found to enhance the psychostimulant-like effects of amphetamine in rodents.

Chemistry

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

References