Mofegiline

Last updated
Mofegiline
Mofegiline.svg
Clinical data
Other namesMDL-72,974A
Routes of
administration
Oral [1]
ATC code
  • None
Legal status
Legal status
  • Development terminated
Pharmacokinetic data
Elimination half-life 1–3 hours [1]
Excretion Urine [2]
Identifiers
  • (2E)-2-(fluoromethylidene)-4-(4-fluorophenyl)butan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
Formula C11H13F2N
Molar mass 197.229 g·mol−1
3D model (JSmol)
  • Fc1ccc(cc1)CCC(=[C@H]F)CN
  • InChI=1S/C11H13F2N/c12-7-10(8-14)2-1-9-3-5-11(13)6-4-9/h3-7H,1-2,8,14H2/b10-7+
  • Key:VXLBSYHAEKDUSU-JXMROGBWSA-N

Mofegiline (MDL-72,974) is a selective, irreversible inhibitor of monoamine oxidase B (MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) which was under investigation for the treatment of Parkinson's disease and Alzheimer's disease, [3] [4] [5] [6] but was never marketed. [7]

See also

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">Monoamine neurotransmitter</span> Monoamine that acts as a neurotransmitter or neuromodulator

Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.

<span class="mw-page-title-main">Phenethylamine</span> Organic compound, a stimulant in humans

Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.

<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.

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

Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl, Emsam, Selgin, among other names, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or tablet taken by mouth or orally disintegrating tablets taken on the tongue for Parkinson's disease and as a patch applied to skin for depression.

<span class="mw-page-title-main">Isocarboxazid</span> Antidepressant

Isocarboxazid is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant. Along with phenelzine and tranylcypromine, it is one of only three classical MAOIs still available for clinical use in the treatment of psychiatric disorders in the United States, though it is not as commonly employed in comparison to the others.

<span class="mw-page-title-main">Moclobemide</span> Antidepressant

Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in the United States, but is approved in other Western countries such as Canada, the UK and Australia. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.

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

Tolcapone, sold under the brand name Tasmar, is a medication used to treat Parkinson's disease (PD). It is a selective, potent and reversible nitrocatechol-type inhibitor of the enzyme catechol-O-methyltransferase (COMT). It has demonstrated significant liver toxicity, which has led to suspension of marketing authorisations in a number of countries.

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

Clorgiline (INN), or clorgyline (BAN), is a monoamine oxidase inhibitor (MAOI) structurally related to pargyline which is described as an antidepressant. Specifically, it is an irreversible and selective inhibitor of monoamine oxidase A (MAO-A). Clorgiline was never marketed, but it has found use in scientific research. It has been found to bind with high affinity to the σ1 receptor (Ki = 3.2 nM) and with very high affinity to the I2 imidazoline receptor (Ki = 40 pM).

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

Rasagiline is an irreversible inhibitor of monoamine oxidase-B used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases.

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

Pargyline (brand name Eutonyl) is an irreversible selective monoamine oxidase (MAO)-B inhibitor drug (IC50 for MAO-A is 11.52 nM and for MAO-B is 8.20 nM) It was brought to market in the US and the UK by Abbott in 1963 as an antihypertensive drug branded "Eutonyl". It was one of several MAO inhibitors introduced in the 1960s including nialamide, isocarboxazid, phenelzine, and tranylcypromine. By 2007 the drug was discontinued and as of 2014 there were no generic versions available in the US. In addition to its actions as an MAOI, pargyline has been found to bind with high affinity to the I2 imidazoline receptor (an allosteric site on the MAO enzyme).

<i>N</i>-Methylphenethylamine Chemical compound

N-Methylphenethylamine (NMPEA) is a naturally occurring trace amine neuromodulator in humans that is derived from the trace amine, phenethylamine (PEA). It has been detected in human urine and is produced by phenylethanolamine N-methyltransferase with phenethylamine as a substrate, which significantly increases PEA's effects. PEA breaks down into phenylacetaldehyde which is further broken down into phenylacetic acid by monoamine oxidase. When this is inhibited by monoamine oxidase inhibitors, it allows more of the PEA to be metabolized into nymphetamine (NMPEA) and not wasted on the weaker inactive metabolites.

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

Benzofuranylpropylaminopentane is a drug with an unusual monoamine-release potentiating mechanism of action. It can loosely be grouped with the stimulant or antidepressant drug families, but its mechanism of action is quite different.

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

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

<span class="mw-page-title-main">AOC3</span> Enzyme

Amine oxidase, copper containing 3 (AOC3), also known as vascular adhesion protein (VAP-1) and HPAO is an enzyme that in humans is encoded by the AOC3 gene on chromosome 17. This protein is a member of the semicarbazide-sensitive amine oxidase family of enzymes and is associated with many vascular diseases.

<span class="mw-page-title-main">Safinamide</span> Reversible monoamine oxidase B inhibitor

Safinamide is a drug used as an add-on treatment for Parkinson's disease with "off" episodes; it has multiple modes of action, including the inhibition of monoamine oxidase B.

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

Ladostigil (TV-3,326) is a novel neuroprotective agent being investigated for the treatment of neurodegenerative disorders like Alzheimer's disease, Lewy body disease, and Parkinson's disease. It acts as a reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor, and combines the mechanisms of action of older drugs like rivastigmine and rasagiline into a single molecule. In addition to its neuroprotective properties, ladostigil enhances the expression of neurotrophic factors like GDNF and BDNF, and may be capable of reversing some of the damage seen in neurodegenerative diseases via the induction of neurogenesis. Ladostigil also has antidepressant effects, and may be useful for treating comorbid depression and anxiety often seen in such diseases as well.

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

Amiflamine (FLA-336) is a reversible inhibitor of monoamine oxidase A (MAO-A), thereby being a RIMA, and, to a lesser extent, semicarbazide-sensitive amine oxidase (SSAO), as well as a serotonin releasing agent (SRA). It is a derivative of the phenethylamine and amphetamine chemical classes. The (+)-enantiomer is the active stereoisomer.

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

Almoxatone (MD-780,236) is a selective and reversible inhibitor of MAO-B. It was patented as an antidepressant and antiparkinsonian agent but was never marketed.

<span class="mw-page-title-main">Moussa B. H. Youdim</span> Iranian scientist

Moussa B. H. Youdim is an internationally renowned 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.

References

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  2. Dulery BD, Schoun J, Zreika M, et al. (March 1993). "Pharmacokinetics of and monoamine oxidase B inhibition by (E)-4-fluoro-beta-fluoromethylene benzene butanamine in man". Arzneimittel-Forschung. 43 (3): 297–302. PMID   8489556.
  3. Palfreyman MG, McDonald IA, Bey P, Schechter PJ, Sjoerdsma A (1988). "Design and early clinical evaluation of selective inhibitors of monoamine oxidase". Progress in Neuro-psychopharmacology & Biological Psychiatry. 12 (6): 967–87. doi:10.1016/0278-5846(88)90092-9. PMID   3266532. S2CID   32734728.
  4. Zreika M, Fozard JR, Dudley MW, Bey P, McDonald IA, Palfreyman MG (1989). "MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease". Journal of Neural Transmission. Parkinson's Disease and Dementia Section. 1 (4): 243–54. doi:10.1007/bf02263478. PMID   2597310. S2CID   26335432.
  5. Palfreyman MG, McDonald IA, Bey P, Danzin C, Zreika M, Cremer G (1994). "Haloallylamine inhibitors of MAO and SSAO and their therapeutic potential". Amine Oxidases: Function and Dysfunction. Journal of Neural Transmission. Supplementum. Vol. 41. pp. 407–14. doi:10.1007/978-3-7091-9324-2_54. ISBN   978-3-211-82521-1. PMID   7931257.
  6. Thiffault C, Quirion R, Poirier J (March 1998). "Effect of the MAO-B inhibitor, MDL72974, on superoxide dismutase activity and lipid peroxidation levels in the mouse brain". Synapse. 28 (3): 208–11. doi:10.1002/(SICI)1098-2396(199803)28:3<208::AID-SYN3>3.0.CO;2-E. PMID   9488505. S2CID   20976168.
  7. Ganellin CR, Triggle DJ, Macdonald F (1997). Dictionary of pharmacological agents. CRC Press. p. 1370. ISBN   978-0-412-46630-4 . Retrieved 25 November 2011.