HDMP-28

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.

HDMP-28 and CFT overlay
HDMP-28
Legal status
Legal status
Identifiers
IUPAC name
  • Methyl (naphthalen-2-yl)(piperidin-2-yl)acetate
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC18H21NO2
Molar mass283.365 g·mol−1
3D model (JSmol)
SMILES
  • O=C(OC)[C@H](C1=CC2=C(C=C1)C=CC=C2)[C@]3([H])CCCCN3

  • O=C(OC)[C@H](c2cc1ccccc1cc2)[C@@H]3NCCCC3
InChI
  • InChI=1S/C18H21NO2/c1-21-18(20)17(16-8-4-5-11-19-16)15-10-9-13-6-2-3-7-14(13)12-15/h2-3,6-7,9-10,12,16-17,19H,4-5,8,11H2,1H3/t16-,17-/m1/s1 N
  • Key:DNRNSIJBSCBESJ-IAGOWNOFSA-N N
 NY (what is this?)  (verify)

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.[2]

aEffect of (dl-threo) TMP and analogs on DA and 5HT Transporters.
Inhibition of specific analogs at displacing CFT from binding to DAT & RTI-55 from binding to SERT
Ar [3H]CFT DAT [3H]DA Uptake [3H]RTI-55 SERT Inhibition by 10μM D.R. Potency
Ph83.9224>>10,00019.62.71.00
p-F35.0142>10,00036.94.13.33
m-Cl5.123.0>10,00045.54.52.42
p-Me33.0126>10,00045.03.80.74
p-NH234.5114>>10,0007.93.32.18
m,p-Cl25.3 (2.67)b7.01,064 (>10,000)b93.31.37.98
β-Naphthyl33.9b 11.0c53.0c71.6bnd4.8c—
Cocaine160404401nd2.50.41
aSchweri, et al. (2002);[3] bDavies, et al. (2004);[4] cDeutsch, et al. (2001).[5]

D.R. = Discrimination Ratio = [3H]DA ÷ [3H]CFT.

A low D.R. = addictive, whereas a high D.R. = low propensity for self-administration.

Legality

HDMP-28 is illegal in Switzerland as of December 2015.[6]

See also

References
  1. Lile JA, Wang Z, Woolverton WL, France JE, Gregg TC, Davies HM, Nader MA (October 2003). "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. doi:10.1124/jpet.103.049825. PMID 12954808. S2CID 5654856.
  2. Davies HM, Hopper DW, Hansen T, Liu Q, Childers SR (April 2004). "Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites". Bioorganic & Medicinal Chemistry Letters. 14 (7): 1799–802. doi:10.1016/j.bmcl.2003.12.097. PMID 15026075.
  3. Schweri MM, Deutsch HM, Massey AT, Holtzman SG (May 2002). "Biochemical and behavioral characterization of novel methylphenidate analogs". The Journal of Pharmacology and Experimental Therapeutics. 301 (2): 527–35. doi:10.1124/jpet.301.2.527. PMID 11961053.
  4. Davies HM, Hopper DW, Hansen T, Liu Q, Childers SR (April 2004). "Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites". Bioorganic & Medicinal Chemistry Letters. 14 (7): 1799–802. doi:10.1016/j.bmcl.2003.12.097. PMID 15026075.
  5. Deutsch HM, Ye X, Shi Q, Liu Z, Schweri MM (April 2001). "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. doi:10.1016/s0223-5234(01)01230-2. PMID 11461755.
  6. "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien". Der Bundesrat.
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