Clorgiline

Clorgiline
Clinical data
Other namesClargyline
Drug classMonoamine oxidase inhibitor; MAO-A inhibitor
ATC code
  • None
Legal status
Legal status
  • In general: uncontrolled
Identifiers
  • N-[3-(2,4-dichlorophenoxy)propyl]-N-methyl-prop-2-yn-1-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC13H15Cl2NO
Molar mass272.17 g·mol−1
3D model (JSmol)
  • Clc1cc(Cl)ccc1OCCCN(CC#C)C
  • InChI=1S/C13H15Cl2NO/c1-3-7-16(2)8-4-9-17-13-6-5-11(14)10-12(13)15/h1,5-6,10H,4,7-9H2,2H3 Y
  • Key:BTFHLQRNAMSNLC-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Clorgiline (INNTooltip International Nonproprietary Name), or clorgyline (BANTooltip British Approved Name), is a monoamine oxidase inhibitor (MAOI) and investigational antidepressant related to pargyline.[1][2] Specifically, it is an irreversible and selective inhibitor of monoamine oxidase A (MAO-A).[3] Clorgiline was never marketed,[1] but it has found use in scientific research.[4]

In addition to its MAOI activity, it has been found to bind with high affinity to the σ1 receptor (Ki = 3.2–510 nM)[5][6][7][8][9] and with very high affinity to the imidazoline I2 receptor (Ki = 40 pM).[10] Unlike selegiline, clorgiline does not appear to be a monoaminergic activity enhancer (MAE).[11][12][13][14]

Clorgiline is also a multidrug efflux pump inhibitor.[15] Holmes et al., 2012 reverse azole fungicide resistance using clorgiline, showing promise for its use in multiple fungicide resistance.[15]

References

  1. ^ a b Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 304–. ISBN 978-1-4757-2085-3.
  2. ^ Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 80–. ISBN 978-94-011-4439-1.
  3. ^ Stone TW (January 1993). Acetylcholine, Sigma Receptors, CCK and Eicosanoids, Neurotoxins. Taylor & Francis. pp. 124–. ISBN 978-0-7484-0063-8.
  4. ^ Murphy DL, Karoum F, Pickar D, Cohen RM, Lipper S, Mellow AM, et al. (1998). "Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (Clorgyline) or MAO-B (Selegiline and pargyline)". MAO — the Mother of all Amine Oxidases. Journal of Neural Transmission. Supplement. Vol. 52. pp. 39–48. doi:10.1007/978-3-7091-6499-0_5. ISBN 978-3-211-83037-6. PMID 9564606.
  5. ^ Itzhak Y (1994). "Multiple sigma binding sites in the brain". In Itzhak Y (ed.). Sigma Receptors. Neuroscience Perspectives. Elsevier Science. pp. 113–137 (118). ISBN 978-0-12-376350-1.
  6. ^ De Costa BR, He XS (1994). "Structure-activity relationships and evolution of sigma receptor ligands (1976-present)". In Itzhak Y (ed.). Sigma Receptors. Neuroscience Perspectives. Elsevier Science. pp. 45–111 (84). ISBN 978-0-12-376350-1.
  7. ^ Itzhak Y, Kassim CO (January 1990). "Clorgyline displays high affinity for sigma binding sites in C57BL/6 mouse brain". Eur J Pharmacol. 176 (1): 107–108. doi:10.1016/0014-2999(90)90139-w. PMID 2155796.
  8. ^ Itzhak Y, Stein I (1990). "Sigma binding sites in the brain; an emerging concept for multiple sites and their relevance for psychiatric disorders". Life Sci. 47 (13): 1073–1081. doi:10.1016/0024-3205(90)90165-n. PMID 2172677.
  9. ^ Itzhak Y, Stein I, Zhang SH, Kassim CO, Cristante D (April 1991). "Binding of sigma-ligands to C57BL/6 mouse brain membranes: effects of monoamine oxidase inhibitors and subcellular distribution studies suggest the existence of sigma-receptor subtypes". J Pharmacol Exp Ther. 257 (1): 141–148. doi:10.1016/S0022-3565(25)24697-3. PMID 1850463.
  10. ^ Piletz JE, Halaris A, Ernsberger PR (1994). "Psychopharmacology of imidazoline and alpha 2-adrenergic receptors: implications for depression". Critical Reviews in Neurobiology. 9 (1): 29–66 (43). PMID 8828003.
  11. ^ Shimazu S, Miklya I (May 2004). "Pharmacological studies with endogenous enhancer substances: β-phenylethylamine, tryptamine, and their synthetic derivatives". Prog Neuropsychopharmacol Biol Psychiatry. 28 (3): 421–427. doi:10.1016/j.pnpbp.2003.11.016. PMID 15093948.
  12. ^ Knoll J (1983). "Deprenyl (selegiline): the history of its development and pharmacological action". Acta Neurol Scand Suppl. 95: 57–80. doi:10.1111/j.1600-0404.1983.tb01517.x. PMID 6428148.
  13. ^ Knoll J (May 1992). "The pharmacological profile of (-)deprenyl (selegiline) and its relevance for humans: a personal view". Pharmacology & Toxicology. 70 (5 Pt 1): 317–321. doi:10.1111/j.1600-0773.1992.tb00480.x. PMID 1608919.
  14. ^ Yen TT, Dalló J, Knoll J (1982). "The aphrodisiac effect of low doses of (-) deprenyl in male rats". Pol J Pharmacol Pharm. 34 (5–6): 303–308. PMID 6821215.
  15. ^ a b