“HDMP-28”的意思、由来-开放百科全书

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.

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 also 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

[³H]CFT DAT

[³H]DA Uptake

[³H]RTI-55 SERT

Inhibition by 10μM

D.R.

Potency

83.9

224

>>10,000

19.6

2.7

1.00

p-F

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

p-Me

33.0

126

>10,000

45.0

3.8

0.74

p-NH₂

34.5

114

>>10,000

7.9

3.3

2.18

m,p-Cl₂

5.3 (2.67)^b

7.0

1,064 (>10,000)^b

93.3

1.3

7.98

β-Naphthyl

33.9^b 11.0^c

53.0^c

71.6^b

4.8^c

—

Cocaine

160

404

401

2.5

0.41

^aSchweri, et al. (2002);^[3] ^bDavies, et al. (2004);^[4] ^cDeutsch, et al. (2001).^[5]

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

Legality

See also

References

1. ^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. Journal of Pharmacology and Experimental Therapeutics. 2003 Oct;307(1):356-66. {{PMID|12954808}}
2. ^Davies HM, Hopper DW, Hansen T, Liu Q, Childers SR. Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites. Bioorg Med Chem Lett. 2004 Apr 5;14(7):1799-802. {{DOI|10.1016/j.bmcl.2003.12.097}} {{PMID|15026075}}
3. ^Schweri MM, Deutsch HM, Massey AT, Holtzman SG. Biochemical and behavioral characterization of novel methylphenidate analogs. J Pharmacol Exp Ther. 2002 May;301(2):527-35. {{DOI|10.1124/jpet.301.2.527}} {{PMID|11961053}}
4. ^Davies HM, Hopper DW, Hansen T, Liu Q, Childers SR. Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites. Bioorg Med Chem Lett. 2004 Apr 5;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. Synthesis and pharmacology of site specific cocaine abuse treatment agents: a new synthetic methodology for methylphenidate analogs based on the Blaise reaction. Eur J Med Chem. 2001 Apr;36(4):303-11. {{PMID|11461755}}
6. ^{{cite web | url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html | title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien | publisher=Der Bundesrat}}