(1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

(1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction. / Pan, Yue; Gerasimov, Madina R; Kvist, Trine; Wellendorph, Petrine; Madsen, Karsten Kirkegaard; Pera, Elena; Lee, Hyunbeom; Schousboe, Arne; Chebib, Mary; Bräuner-Osborne, Hans; Craft, Cheryl M; Brodie, Jonathan D; Schiffer, Wynne K; Dewey, Stephen L; Miller, Stephen R; Silverman, Richard B.

In: Journal of Medicinal Chemistry, Vol. 55, No. 1, 01.01.2012, p. 357-366.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Pan, Y, Gerasimov, MR, Kvist, T, Wellendorph, P, Madsen, KK, Pera, E, Lee, H, Schousboe, A, Chebib, M, Bräuner-Osborne, H, Craft, CM, Brodie, JD, Schiffer, WK, Dewey, SL, Miller, SR & Silverman, RB 2012, '(1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction', Journal of Medicinal Chemistry, vol. 55, no. 1, pp. 357-366. https://doi.org/10.1021/jm201231w

APA

Pan, Y., Gerasimov, M. R., Kvist, T., Wellendorph, P., Madsen, K. K., Pera, E., ... Silverman, R. B. (2012). (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction. Journal of Medicinal Chemistry, 55(1), 357-366. https://doi.org/10.1021/jm201231w

Vancouver

Pan Y, Gerasimov MR, Kvist T, Wellendorph P, Madsen KK, Pera E et al. (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction. Journal of Medicinal Chemistry. 2012 Jan 1;55(1):357-366. https://doi.org/10.1021/jm201231w

Author

Pan, Yue ; Gerasimov, Madina R ; Kvist, Trine ; Wellendorph, Petrine ; Madsen, Karsten Kirkegaard ; Pera, Elena ; Lee, Hyunbeom ; Schousboe, Arne ; Chebib, Mary ; Bräuner-Osborne, Hans ; Craft, Cheryl M ; Brodie, Jonathan D ; Schiffer, Wynne K ; Dewey, Stephen L ; Miller, Stephen R ; Silverman, Richard B. / (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 1. pp. 357-366.

Bibtex

@article{9a6aba43d4014056aafb96c03fde26fb,
title = "(1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction",
abstract = "Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off-target activities and is rapidly and completely orally absorbed and eliminated. Using in vivo microdialysis techniques in freely moving rats and micro-PET imaging techniques, CPP-115 produced similar inhibition of cocaine-induced increases in extracellular dopamine and in synaptic dopamine in the nucleus accumbens at 1/300-1/600th the dose of vigabatrin. It also blocks expression of cocaine-induced conditioned place preference at a dose 1/300th that of vigabatrin. Electroretinographic (ERG) responses in rats treated with CPP-115, at doses 20-40 times higher than those needed to treat addiction in rats, exhibited reductions in ERG responses, which were less than the reductions observed in rats treated with vigabatrin at the same dose needed to treat addiction in rats. In conclusion, CPP-115 can be administered at significantly lower doses than vigabatrin, which suggests a potential new treatment for addiction with a significantly reduced risk of visual field defects.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Yue Pan and Gerasimov, {Madina R} and Trine Kvist and Petrine Wellendorph and Madsen, {Karsten Kirkegaard} and Elena Pera and Hyunbeom Lee and Arne Schousboe and Mary Chebib and Hans Br{\"a}uner-Osborne and Craft, {Cheryl M} and Brodie, {Jonathan D} and Schiffer, {Wynne K} and Dewey, {Stephen L} and Miller, {Stephen R} and Silverman, {Richard B}",
note = "Keywords: GABA aminotransferase; enzyme inactivator; addiction; cocaine; visual field defect; pharmacokinetics; micro-PET imaging; conditioned place preference",
year = "2012",
month = "1",
day = "1",
doi = "10.1021/jm201231w",
language = "English",
volume = "55",
pages = "357--366",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "1",

}

RIS

TY - JOUR

T1 - (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction

AU - Pan, Yue

AU - Gerasimov, Madina R

AU - Kvist, Trine

AU - Wellendorph, Petrine

AU - Madsen, Karsten Kirkegaard

AU - Pera, Elena

AU - Lee, Hyunbeom

AU - Schousboe, Arne

AU - Chebib, Mary

AU - Bräuner-Osborne, Hans

AU - Craft, Cheryl M

AU - Brodie, Jonathan D

AU - Schiffer, Wynne K

AU - Dewey, Stephen L

AU - Miller, Stephen R

AU - Silverman, Richard B

N1 - Keywords: GABA aminotransferase; enzyme inactivator; addiction; cocaine; visual field defect; pharmacokinetics; micro-PET imaging; conditioned place preference

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off-target activities and is rapidly and completely orally absorbed and eliminated. Using in vivo microdialysis techniques in freely moving rats and micro-PET imaging techniques, CPP-115 produced similar inhibition of cocaine-induced increases in extracellular dopamine and in synaptic dopamine in the nucleus accumbens at 1/300-1/600th the dose of vigabatrin. It also blocks expression of cocaine-induced conditioned place preference at a dose 1/300th that of vigabatrin. Electroretinographic (ERG) responses in rats treated with CPP-115, at doses 20-40 times higher than those needed to treat addiction in rats, exhibited reductions in ERG responses, which were less than the reductions observed in rats treated with vigabatrin at the same dose needed to treat addiction in rats. In conclusion, CPP-115 can be administered at significantly lower doses than vigabatrin, which suggests a potential new treatment for addiction with a significantly reduced risk of visual field defects.

AB - Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off-target activities and is rapidly and completely orally absorbed and eliminated. Using in vivo microdialysis techniques in freely moving rats and micro-PET imaging techniques, CPP-115 produced similar inhibition of cocaine-induced increases in extracellular dopamine and in synaptic dopamine in the nucleus accumbens at 1/300-1/600th the dose of vigabatrin. It also blocks expression of cocaine-induced conditioned place preference at a dose 1/300th that of vigabatrin. Electroretinographic (ERG) responses in rats treated with CPP-115, at doses 20-40 times higher than those needed to treat addiction in rats, exhibited reductions in ERG responses, which were less than the reductions observed in rats treated with vigabatrin at the same dose needed to treat addiction in rats. In conclusion, CPP-115 can be administered at significantly lower doses than vigabatrin, which suggests a potential new treatment for addiction with a significantly reduced risk of visual field defects.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/jm201231w

DO - 10.1021/jm201231w

M3 - Journal article

C2 - 22128851

VL - 55

SP - 357

EP - 366

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 1

ER -

ID: 35438191