LY-134046
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| Other names | SKF-81981 |
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| Formula | C10H11Cl2N |
| Molar mass | 216.11 g·mol−1 |
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LY-134046 is a synthetic organic compound known as a potent and selective inhibitor of phenylethanolamine N-methyltransferase (PNMT), the enzyme responsible for converting norepinephrine to epinephrine.[1][2]
Animal studies
LY-134046 has several potential therapeutic indications based on its pharmacological profile as a selective inhibitor of phenylethanolamine-N-methyltransferase (PNMT):
Hypertension
LY-134046 may be relevant in the management of high blood pressure, as inhibition of PNMT influences cardiovascular responses by reducing epinephrine synthesis, which can affect blood pressure regulation.[3]
Ethanol intoxication
LY-134046 and related PNMT inhibitors can antagonize ethanol-induced behaviors such as intoxication and sedation, suggesting possible applications in treating alcohol-related disorders.[2]
Neuroendocrine disorders
The compound has been shown to affect hypothalamic neurotransmitter balance and modulate the secretion of hormones like luteinizing hormone (LH), pointing to potential in conditions involving neuroendocrine regulation, such as certain reproductive or hormonal dysfunctions.[4][5]
Behavioral and CNS effects
LY-134046 alters specific behaviors in animal models, hinting that it may modulate brain catecholamine pathways implicated in behavioral disorders or possibly mood regulation.[3][2]
Synthesis
A key step in the synthesis of LY-134046 is an intramolecular cyclization reaction between an amine and ester, which is responsible for constructing the benzazepine core of the molecule.[1][6][7]
See also
References
- ^ a b "LY-134046". Drugs of the Future. 9 (4): 268. 1984. doi:10.1358/dof.1984.009.04.65191. ISSN 0377-8282.
- ^ a b c Durcan MJ, Lister RG, Linnoila M (1990). "Behavioral effects of the inhibitors of phenylethanolamine-N-methyltransferase, LY 78335 and LY 134046, and their interactions with ethanol". Psychopharmacology. 101 (2): 196–202. doi:10.1007/BF02244126. PMID 2349361.
- ^ a b Mefford IN, Lawrenz AL, Hsiao JK, Crawley JN (1989). "Activation in young rats induced by LY134046, an inhibitor of phenylethanolamine N-methyltransferase". Psychopharmacology. 98 (2): 240–4. doi:10.1007/BF00444698. PMID 2502794.
- ^ Steele MK, Ganong WF (December 1986). "Effects of catecholamine-depleting agents and receptor blockers on basal and angiotensin II- or norepinephrine-stimulated luteinizing hormone release in female rats". Endocrinology. 119 (6): 2728–36. doi:10.1210/endo-119-6-2728. PMID 3023020.
- ^ Gallo RV, Bona-Gallo A, O'Sullivan D (June 1989). "Adrenergic and noradrenergic regulation of pulsatile luteinizing hormone release". Journal of Neuroendocrinology. 1 (3): 157–62. doi:10.1111/j.1365-2826.1989.tb00096.x. PMID 19210448.
- ^ Grunewald GL, Paradkar VM (January 1991). "A regioselective synthesis of 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine (LY134046), a potent phenylethanolamine N-methyltransferase inhibitor". Bioorganic & Medicinal Chemistry Letters. 1 (1): 59–60. doi:10.1016/S0960-894X(01)81091-X.
- ^ Perchonock CD, Lantos I, Finkelstein JA, Holden KG (May 1980). "Facile synthesis of halo-substituted tetrahydroisoquinolines and tetrahydro-2-benzazepines via N-acetyl-1,2-dihydroisoquinolines". The Journal of Organic Chemistry. 45 (10): 1950–1953. doi:10.1021/jo01298a038.