(''R'')-1-Aminoindane ((''R'')-1-AI; developmental code name TVP-136 or TV-136), or (''R'')-1-aminoindan, is the major

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of the selective

MAO-B inhibitor 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, espec ...

and

antiparkinsonian agent In the management of Parkinson's disease, due to the chronic nature of Parkinson's disease (PD), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutr ...

rasagiline 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 advan ...

((''R'')-''N''-propargyl-1-aminoindane). In contrast to rasagiline, it lacks significant

monoamine oxidase inhibition 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, especia ...

. In addition, unlike selegiline and its

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

s, it lacks monoamine reuptake-inhibiting and -releasing activities and associated

-like

psychostimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...

effects. However, (''R'')-1-aminoindane retains

neuroprotective Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal l ...

effects and certain other activities.

Pharmacology

Pharmacodynamics

In contrast to rasagiline, (''R'')-1-aminoindane is either devoid of

or shows only weak

inhibition Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransm ...

MAO-B Monoamine oxidase B (MAO-B) is an enzyme that in humans is encoded by the ''MAOB'' gene. The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. It catalyze ...

. Unlike selegiline and its

levomethamphetamine Levomethamphetamine (International Nonproprietary Name, INN: levmetamfetamine) is an optical isomer of methamphetamine primarily used as a Topical decongestant, topical nasal decongestant. Levomethamphetamine is used to treat nasal congestion f ...

and

levoamphetamine 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 drug, combination with dextroam ...

s, rasagiline and (''R'')-1-aminoindane have no

-like activity. In spite of the preceding however, (''R'')-1-aminoindane is not lacking in

pharmacological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...

. Like rasagiline, it shows

activity in some experimental models. In addition, (''R'')-1-aminoindane has been found to enhance striatal

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron ...

and to improve

motor An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy. Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power gene ...

function independent of MAO inhibition in

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

s of Parkinson's disease. 2-Aminoindane, a closely related

positional isomer In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a compound is a compound that contains the same number and type of atoms, but with a different connectivity (i.e. arrangement of bonds) between them. The ...

of 1-aminoindane, is known to inhibit the reuptake and induce the release of dopamine and norepinephrine and to produce

-like effects in rodents, albeit with lower

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of ho ...

than

. 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

, 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 In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

. It is specifically the (''R'')-

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

of 1-aminoindane, which is a

racemic mixture In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

of (''R'')- and (''S'')-

s. 1-Aminoindane is structurally related to 2-aminoindan. A number of derivatives of 1- and 2-aminoindane are known.

References

{{DEFAULTSORT:Aminoindane, (R)-1- 1-Aminoindanes Drugs with unknown mechanisms of action Enantiopure drugs Human drug metabolites Neuroprotective agents