HDMP-28 explained
HDMP-28 or methylnaphthidate is a piperidine based stimulant drug, closely related to methylphenidate, but with the benzene ring replaced by naphthalene. It is a potent dopamine reuptake inhibitor, with several times the potency of methylphenidate and a short duration of action,[1] and is a structural isomer of another potent dopamine reuptake inhibitor, N,O-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate. It has been sold as a designer drug since around 2015.[2]
Most of the TMP analogs of HDMP-28 have SERT Ki values in the range >10,000 and so are selective for dopamine and noradrenaline reuptake, with little or no effect on serotonin. HDMP-28 has high affinity to SERT, and so behaves as a triple reuptake inhibitor.[3]
aEffect of (dl-threo) TMP and analogs on DA and 5-HT Transporters.| Inhibition of specific analogs at displacing CFT from binding to DAT & RTI-55 from binding to SERT |
| Ar | [<sup>3</sup>H]CFT DAT | [<sup>3</sup>H]DA Uptake | [<sup>3</sup>H]RTI-55 SERT | Inhibition by 10 μM | | Potency |
|---|
| 83.9 | 224 | ≫10,000 | 19.6 | 2.7 | 1.00 |
| 35.0 | 142 | >10,000 | 36.9 | 4.1 | 3.33 |
| m-Cl | 5.1 | 23.0 | >10,000 | 45.5 | 4.5 | 2.42 |
| 33.0 | 126 | >10,000 | 45.0 | 3.8 | 0.74 |
| p-NH2 | 34.5 | 114 | ≫10,000 | 7.9 | 3.3 | 2.18 |
| 5.3 (2.67)b | 7.0 | 1,064 (>10,000)b | 93.3 | 1.3 | 7.98 |
| β-Naphthyl | 33.9b 11.0c | 53.0c | 71.6b | | 4.8c | — |
| 160 | 404 | 401 | nd | 2.5 | 0.41 |
| aSchweri, et al. (2002);[4] bDavies, et al. (2004);[5] cDeutsch, et al. (2001).[6] | |
D.R. is the discrimination ratio = [3H]DA ÷ [3H]CFT.
A low D.R. indicates more addictive, whereas a high D.R. indicates low propensity for self-administration.
Legality
HDMP-28 is illegal in Switzerland as of December 2015.[7]
See also
Further reading
- Muhammed Ajeebsanu M, Subhahar MB, Karakka Kal AK, Philip M, Perwad Z, Karatt TK, Graiban FM, Joseph M, Jose SV . Comprehensive metabolic investigation of dopamine reuptake inhibitor HDMP-28 in equine liver microsomes and Cunninghamella elegans for doping control . Drug Testing and Analysis . January 2024 . 38225724 . 10.1002/dta.3642 .
Notes and References
- Lile JA, Wang Z, Woolverton WL, France JE, Gregg TC, Davies HM, Nader MA . The reinforcing efficacy of psychostimulants in rhesus monkeys: the role of pharmacokinetics and pharmacodynamics . The Journal of Pharmacology and Experimental Therapeutics . 307 . 1 . 356–66 . October 2003 . 12954808 . 10.1124/jpet.103.049825 . 5654856 .
- Carlier J, Giorgetti R, Varì MR, Pirani F, Ricci G, Busardò FP . Use of cognitive enhancers: methylphenidate and analogs . European Review for Medical and Pharmacological Sciences . 23 . 1 . 3–15 . January 2019 . 30657540 . 10.26355/eurrev_201901_16741 .
- Davies HM, Hopper DW, Hansen T, Liu Q, Childers SR . Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites . Bioorganic & Medicinal Chemistry Letters . 14 . 7 . 1799–802 . April 2004 . 15026075 . 10.1016/j.bmcl.2003.12.097 .
- Schweri MM, Deutsch HM, Massey AT, Holtzman SG . Biochemical and behavioral characterization of novel methylphenidate analogs . The Journal of Pharmacology and Experimental Therapeutics . 301 . 2 . 527–35 . May 2002 . 11961053 . 10.1124/jpet.301.2.527 .
- Davies HM, Hopper DW, Hansen T, Liu Q, Childers SR . Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites . Bioorganic & Medicinal Chemistry Letters . 14 . 7 . 1799–802 . April 2004 . 15026075 . 10.1016/j.bmcl.2003.12.097 .
- Deutsch HM, Ye X, Shi Q, Liu Z, Schweri MM . Synthesis and pharmacology of site specific cocaine abuse treatment agents: a new synthetic methodology for methylphenidate analogs based on the Blaise reaction . European Journal of Medicinal Chemistry . 36 . 4 . 303–11 . April 2001 . 10.1016/s0223-5234(01)01230-2 . 11461755 .
- Web site: Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien . Ordinance of the Federal Department of Home Affairs on the lists of narcotics, psychotropic substances, precursors and auxiliary chemicals . de . Der Bundesrat (The Federal Council) .
