H77/77

H77/77
Clinical data
Drug classSNDRA; monoamine oxidase inhibitor; monoamine-depleting agent (dopamine-- norepineprine- serotonin-depleting agent)
ATC code
  • None
Identifiers
  • 5-(2-aminopropyl)-2-methylphenol
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC10H15NO2
Molar mass181.235 g·mol−1
3D model (JSmol)
  • CC1=C(C=C(C=C1)CC(C)N)O
  • InChI=1S/C10H15NO/c1-7-3-4-9(5-8(2)11)6-10(7)12/h3-4,6,8,12H,5,11H2,1-2H3
  • Key:XWLXNPMITZDCHL-UHFFFAOYSA-N

H77/77 It is a stimulant drug belonging to the substituted amphetamine class, which acts as a monoamine oxidase inhibitor and a monoamine releasing agent, and was first developed in the second half of the 20th century to study its effects on monoamines.

Pharmacology

Pharmacodynamics

H77/77 acts as a serotonin–norepinephrine–dopamine releasing agent; this is supported by the fact that H77/77-induced hyperthermia is effectively blocked by milnacipran, and that high doses of modafinil can significantly counteract the effect and protect dopamine stores from H77/77-induced depletion. Furthermore, cianopramine, citalopram, and related compounds have been shown to antagonize H77/77-induced 5-HT displacement in the rat brain. H77/77 caused brain norepinephrine depletion; at least when combined with dextrorotatory isomers of amphetamine and methamphetamine, this potentiated the effect. Following the synthesis of H77/77 in 1969 by Arvid Carlsson and his research group, it was reported that H77/77 displaces catecholamines, particularly norepinephrine, from the brain and utilizes a reserpine-resistant uptake mechanism for this displacement, which was verified via injection of H77/77 into animals: in a study by Brian E. Leonard and colleagues. The drug induced dopamine depletion that was unaffected by either dextroamphetamine or dextromethamphetamine, whereas para-bromomethamphetamine prevented the H77/77-induced dopamine depletion. Brain catecholamine depletion was measured by the levels of norepinephrine and dopamine following drug administration. The baseline levels in the rat brain were 0.58 ± 0.012 µg/g for norepinephrine and 0.94 ± 0.084 µg/g for dopamine. After the administration of drugs such as dextroamphetamine and dextromethamphetamine, norepinephrine levels dropped to an extremely low 0.22 ± 0.015 µg/g for the mixture of D-amphetamine and H77/77, and to 0.25 ± 0.012 µg/g for the mixture of D-methamphetamine, respectively; moreover, H77/77-induced reduction of norepinephrine was equal to 0.37 ± 0.054 µg/g, and 0.66 ± 0.047 µg/g for dopamine. H77/77 also provides marked protection of the monoamine oxidase enzymes against irreversible inhibition by phenelzine. This mechanism functions effectively specifically within serotonergic and norepinephrinergic neurons.

References

  1. ↑ Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M (December 1985). "Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug". Neuropharmacology. 24 (12): 1211–1219. doi:10.1016/0028-3908(85)90157-1. PMID 3005901.
  2. ↑ Fuxe K, Janson AM, Rosén L, Finnman UB, Tanganelli S, Morari M, et al. (1992). "Evidence for a protective action of the vigilance promoting drug modafinil on the MPTP-induced degeneration of the nigrostriatal dopamine neurons in the black mouse: an immunocytochemical and biochemical analysis". Experimental Brain Research. 88 (1): 117–130. doi:10.1007/BF02259133. PMID 1347270.
  3. ↑ Pawlowski L, Nowak G, Górka Z, Mazela H (1985). "Ro 11-2465 (cyan-imipramine), citalopram and their N-desmethyl metabolites: effects on the uptake of 5-hydroxytryptamine and noradrenaline in vivo and related pharmacological activities". Psychopharmacology. 86 (1–2). Berl: 156–163. doi:10.1007/BF00431702. PMID 3927352.
  4. ↑ Carlsson A, Fuxe K, Hamberger B, Malmfors T (May 1969). "Effect of a new series of bicyclic compounds with potential thymoleptic properties on the reserpine-resistant uptake mechanism of central and peripheral monoamine neurones in vivo and in vitro". British Journal of Pharmacology. 36 (1): 18–28. doi:10.1111/j.1476-5381.1969.tb08299.x. PMC 1703539. PMID 5768100.
  5. 1 2 Leonard BE, Shallice SA (February 1971). "Some neurochemical effects of amphetamine, methylamphetamine and p-bromomethylamphetamine in the rat". British Journal of Pharmacology. 41 (2): 198–212. doi:10.1111/j.1476-5381.1971.tb08022.x. PMC 1703283. PMID 5572273.
  6. ↑ Fagervall I, Kelder D, Ross SB (August 1988). "Selective inhibition by 4,alpha-dimethyl-m-tyramine (H77/77) and 4-methyl-alpha-ethyl-m-tyramine (H75/12) of the monoamine oxidase within serotonergic and noradrenergic neurons in the rat brain". Naunyn-Schmiedeberg's Archives of Pharmacology. 338 (2): 143–147. doi:10.1007/BF00174862. PMID 2460774.