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Sunday, March 3, 2013

Biological Actions of Various Pyrovalerone-Family Compounds on Monoamine Systems

Very Potent NDRI's Indeed:

Ki Values indicate binding affinity

IC50 values indicate level of intrinsic activity (measured by the amount of a given compound it takes to inhibit the function of a monoamine transporter by 50%)

DAT/DA = Dopamine 
NET/NE = Norepinephrine
SERT/SER = Serotonin

Cocaine (Reference Standard)
DAT Ki: 432 ± 29
DA IC50: 461 ± 46

NET Ki: 2150 ± 190
NE IC50: 378 ± 48

SERT Ki: 358 ± 24
SER IC50: 494 ± 51

APVP
DAT Ki: 33.7 ± 5.4
DA IC50: 52.3 ± 6.2

NET Ki: 199 ± 45
NE IC50: 56.0 ± 13

SERT Ki: >10┬ÁM
SER IC50: ???

Pyrovalerone (Racemic)
DAT Ki: 21.4 ± 4.6
DA IC50: 52.0 ± 20

NET Ki: 195 ± 26
NE IC50: 28.3 ± 8.1

SERT Ki: 3770 ± 560
SER IC50: 2780 ± 590

S-Pyrovalerone 
DAT Ki: 18.1 ± 3.0
DA IC50: 16.3 ± 2.3

NET Ki: 109 ± 45
NE IC50: 11.3 ± 2.4

SERT Ki: 2220 ± 550
SER IC50: 1070 ± 230

Naphyrone
DAT Ki: 20.1 ± 7.1
DA IC50: 40.0 ± 13

SERT Ki: 33.1 ± 1.1
SER IC50: 46.0 ± 5.5

NET Ki: 136 ± 27
NE IC50: 11.7 ± 0.9

3,4-Dichloropyrovalerone 
DAT Ki: 11.5 ± 1.4
DA IC50: 43.0 ± 20

SERT Ki: 199 ± 50
SER IC50: 600 ± 63

NET Ki: 37.8 ± 3.2
NE IC50: 21.0 ± 0.6


Meltzer PC, Butler D, Deschamps JR, Madras BK. 1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) analogues: a promising class of monoamine uptake inhibitors. Journal of Medicinal Chemistry. 2006 Feb 23;49(4):1420-32.

PMID: 16480278
DOI: 10. 1021/jm050797a


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