Clorgiline

Clorgiline
Clinical data
Other names	Clargyline
Drug class	Monoamine oxidase inhibitor; MAO-A inhibitor
ATC code	None;
Legal status
Legal status	In general: uncontrolled;
Identifiers
	IUPAC name N-[3-(2,4-dichlorophenoxy)propyl]-N-methyl-prop-2-yn-1-amine;
CAS Number	17780-72-2 Y;
PubChem CID	4380;
IUPHAR/BPS	6636;
DrugBank	DB04017 Y;
ChemSpider	4227 Y;
UNII	LYJ16FZU9Q;
KEGG	D03248 Y;
ChEBI	CHEBI:3763 N;
ChEMBL	ChEMBL8706 Y;
CompTox Dashboard (EPA)	DTXSID3048445 ;
Chemical and physical data
Formula	C13H15Cl2NO
Molar mass	272.17 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Clc1cc(Cl)ccc1OCCCN(CC#C)C;
	InChI 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.¹² 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 (K_i = 3.2–510 nM)⁵⁶⁷⁸⁹ and with very high affinity to the imidazoline I₂ receptor (K_i = 40 pM).¹⁰ Unlike selegiline, clorgiline does not appear to be a monoaminergic activity enhancer (MAE).¹¹¹²¹³¹⁴

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

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.
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.
Stone TW (January 1993). Acetylcholine, Sigma Receptors, CCK and Eicosanoids, Neurotoxins. Taylor & Francis. pp. 124–. ISBN 978-0-7484-0063-8.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
- • Prasad R, Banerjee A, Shah AH (February 2017). "Resistance to antifungal therapies". Essays in Biochemistry. 61 (1). Portland Press (Biochemical Society): 157–166. CiteSeerX 10.1.1.1066.1806. doi:10.1042/ebc20160067. PMID 28258238. S2CID 3414820.
- • Holmes AR, Keniya MV, Ivnitski-Steele I, Monk BC, Lamping E, Sklar LA, et al. (March 2012). "The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates". Antimicrobial Agents and Chemotherapy. 56 (3). American Society for Microbiology: 1508–1515. doi:10.1128/aac.05706-11. PMC 3294898. PMID 22203607. S2CID 21170509.

[Elks2014-1] 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.

[MortonHall2012-2] 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.

[Stone1993-3] Stone TW (January 1993). Acetylcholine, Sigma Receptors, CCK and Eicosanoids, Neurotoxins. Taylor & Francis. pp. 124–. ISBN 978-0-7484-0063-8.

[MurphyKaroum1998-4] 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.

[Itzhak1994-5] 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.

[DeCostaHe1994-6] 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.

[ItzhakKassim1990-7] 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.

[ItzhakStein1990-8] 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.

[ItzhakSteinZhang1991-9] 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.

[pmid8828003-10] 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.

[ShimazuMiklya2004-11] 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.

[Knoll1983-12] 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.

[Knoll1992-13] 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.

[YenDallóKnoll1982-14] 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.

[Fungus-15] • Prasad R, Banerjee A, Shah AH (February 2017). "Resistance to antifungal therapies". Essays in Biochemistry. 61 (1). Portland Press (Biochemical Society): 157–166. CiteSeerX 10.1.1.1066.1806. doi:10.1042/ebc20160067. PMID 28258238. S2CID 3414820.
• Holmes AR, Keniya MV, Ivnitski-Steele I, Monk BC, Lamping E, Sklar LA, et al. (March 2012). "The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates". Antimicrobial Agents and Chemotherapy. 56 (3). American Society for Microbiology: 1508–1515. doi:10.1128/aac.05706-11. PMC 3294898. PMID 22203607. S2CID 21170509.

[16] • Prasad R, Banerjee A, Shah AH (February 2017). "Resistance to antifungal therapies". Essays in Biochemistry. 61 (1). Portland Press (Biochemical Society): 157–166. CiteSeerX 10.1.1.1066.1806. doi:10.1042/ebc20160067. PMID 28258238. S2CID 3414820.

[17] • Holmes AR, Keniya MV, Ivnitski-Steele I, Monk BC, Lamping E, Sklar LA, et al. (March 2012). "The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates". Antimicrobial Agents and Chemotherapy. 56 (3). American Society for Microbiology: 1508–1515. doi:10.1128/aac.05706-11. PMC 3294898. PMID 22203607. S2CID 21170509.

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