European Journal of Chemistry 2020, 11(1), 84-90 | doi: | Get rights and content

Issue cover



Dopamine antagonists for the treatment of drug addiction: PF-4363467 and related compounds

Ana Martinez (1,*) orcid

(1) Departamento de Materiales de Baja Dimensionalidad, Instituto de Investigaciones en Materiales, Universidad Nacional Autonoma de Mexico, Circuito Exterior S/N, Ciudad Universitaria. Coyoacan, CP 04510, CDMX, Mexico
(*) Corresponding Author

Received: 12 Feb 2020 | Revised: 25 Feb 2020 | Accepted: 28 Feb 2020 | Published: 31 Mar 2020 | Issue Date: March 2020


Drug addiction refers to an out-of-control and compulsive use of substances, which can reach epidemic magnitudes. It is a health concern throughout the world and has major economic impact. Dopamine receptor agonists and antagonists have been cited as molecular targets for the treatment of drug addiction. In this report, the main idea is to analyze the new D3R/D2R ligands that are proposed for the treatment of drug abuse, in terms of their electron donor/acceptor properties. Substances catalogued as agonists represent good electron donors, whereas antagonists represent good electron acceptors. HOMO and LUMO eigenvalues indicate that more energy is necessary to remove an electron from the antagonists, and likewise more energy is gained when antagonists accept an electron. The combination of two molecules (PF-592379 and PNU-177864) produces a new compound (PF-4363467) with properties that are intermediate. Irrespective of the characteristics of the receptor, the classification of ligands is important, in order to further understanding of the reaction mechanism of these compounds. This may help in the design of new molecules for the treatment of drug addiction.


Our editors have decided to support scientists to publish their manuscripts in European Journal of Chemistry without any financial constraints.

1- The article processing fee will not be charged from the articles containing the single-crystal structure characterization between November 15, 2022 and December 28, 2022 (Voucher code: SINGLE2022).

2. Young writers will not be charged for the article processing fee between November 15, 2022 and December 28, 2022 (Voucher code: YOUNG2022).

3. The article processing fee will not be charged from the articles containing a part of the PhD thesis between November 15, 2022 and December 28, 2022 (Voucher code: PhD2022).

4. The article processing fee will not be charged from authors who have at least one publication in the European Journal of Chemistry between November 15, 2022 and December 28, 2022 (Voucher code: (Voucher code: AUTHOR2022).


European Journal of Chemistry


Drug design; Biomolecule; Antipsychotics; Donor acceptor map; Computational chemistry; Density functional calculations

Full Text:

PDF    Open Access

DOI: 10.5155/eurjchem.11.1.84-90.1970

Links for Article

| | | | | |

| | | | | | |

| | | |

Related Articles

Article Metrics

icon graph This Abstract was viewed 1770 times | icon graph PDF Article downloaded 315 times

Funding information

Universidad Nacional Autonoma de Mexico (CONACYT) Coyoacan, Mexico.



[1]. Guillermo Goode-Romero, Ulrika Winnberg, Laura Domínguez, Ilich A. Ibarra, Rubicelia Vargas, Elisabeth Winnberg, Ana Martínez
New information of dopaminergic agents based on quantum chemistry calculations
Scientific Reports  10(1), , 2020
DOI: 10.1038/s41598-020-78446-4

[2]. Ana Martínez, Ponciano García-Gutiérrez, Rafael A. Zubillaga, Jorge Garza, Rubicelia Vargas
Main interactions of dopamine and risperidone with the dopamine D2 receptor
Physical Chemistry Chemical Physics  23(26), 14224, 2021
DOI: 10.1039/D1CP01637G

[3]. Roxana M. Castillo, Estrella Ramos, Ana Martínez
Interaction of graphene with antipsychotic drugs: Is there any charge transfer process?
Journal of Computational Chemistry  42(1), 60, 2021
DOI: 10.1002/jcc.26433

[4]. Guillermo Goode-Romero, Laura Dominguez, Rubicelia Vargas, Ilich A. Ibarra, Ana Martínez
Analyzing the interaction energy between dopaminergic agents and DRD2: Is there any difference between risperidone (antagonist), aripiprazole (partial agonist) and pramipexole (agonist)?
Computational and Theoretical Chemistry  1197, 113125, 2021
DOI: 10.1016/j.comptc.2020.113125

[5]. Ana Martínez, Rubicelia Vargas, Sara E. Pérez-Figueroa, Estrella Ramos
Copper and neurodegenerative disorders: potential drugs for possible successful treatment
Theoretical Chemistry Accounts  140(6), , 2021
DOI: 10.1007/s00214-021-02776-3

[6]. Guillermo Goode-Romero, Laura Dominguez, Ana Martínez
Electron Donor–Acceptor Properties of Different Muscarinic Ligands: On the Road to Control Schizophrenia
Journal of Chemical Information and Modeling  61(10), 5117, 2021
DOI: 10.1021/acs.jcim.1c00780


[1]. National Institute on Drug Abuse, Drugs, Brains, and Behaviour: The Science of Addiction, NIH Publication: USA, 2014.

[2]. Singh, J.; Gupta, P. Inter. J. Indian Psych. 2017, 5, 2348-5396.

[3]. Medina-Mora, M. E.; Cravioto, P.; Ortiz, A.; Kuri, P.; Villatoro, J. Bull. Narcotics. 2003, 55, 105-119.

[4]. Wager, T. T.; Chandrasekaran, R. Y.; Bradley, J.; Rubitski, D.; Berke, H.; Mente, S.; Butler, T.; Doran, A.; Chang, C.; Fisher, K.; Knafels, J.; Liu, S.; Ohren, J.; Marconi, M.; DeMarco, G.; Sneed, B.; Walton, K.; Horton, D.; Rosado, A.; Mead, A. ACS Chem. Neurosci. 2014, 5, 1253-1265.

[5]. Sokoloff, P.; Giros, B.; Martres, M. P.; Bouthenet, M. L.; Schwartz, J. C. Nature 1990, 347, 146-151.

[6]. Newman, A. H.; Grundt, P.; Nader, M. A. J. Med. Chem. 2005, 48, 3663-3679.

[7]. Heidbreder, C. A.; Newman, A. H. Ann. NY Acad. Sci. 2010, 1187, 4-34.

[8]. Cho, D.; Zheng, M.; Kim, K. M. Arch. Pharmacal. Res. 2010, 33, 1521-1538.

[9]. Keck, T. M.; John, W. S.; Czoty, P. W.; Nader, M. A.; Newman, A. H. J. Med. Chem. 2015, 58, 5361-5380.

[10]. Micheli, F.; Arista, L.; Bonanomi, G.; Blaney, F. E.; Braggio, S.; Capelli, A. M.; Checchia, A.; Damiani, F.; Di-Fabio, R.; Fontana, S.; Gentile, G.; Griffante, C.; Hamprecht, D.; Marchioro, C.; Mugnaini, M.; Piner, J.; Ratti, E.; Tedesco, G.; Tarsi, L.; Terreni, S.; Worby, A.; Ashby Jr. , C. R.; Heidbreder, C. J. Med. Chem. 2010, 53, 374-391.

[11]. Mugnaini, M.; Iavarone, L.; Cavallini, P.; Griffante, C.; Oliosi, B.; Savoia, C.; Beaver, J.; Rabiner, E. A.; Micheli, F.; Heidbreder, C.; Andorn, A.; Pich, E. M.; Bani, M. Neuropsychopharmacology 2013, 38, 302-312.

[12]. Pilla, M.; Perachon, S.; Sautel, F.; Garridok, F.; Mannk, A.; Wermuthk, C. G.; Schwartz, J. C.; Everitt, B. J.; Sokoloff, P. Nature 1999, 400, 371-375.

[13]. Le Foll, B.; Goldberg, S. R.; Sokoloff, P. Neuropharmacology 2005, 49, 525-541.

[14]. Roman, V.; Gyertyan, I.; Saghy, K.; Kiss, B.; Szombathelyi, Z. Psychopharmacology 2013, 226, 285-293.

[15]. Li, P.; Snyder, G. L.; Vanover, K. E. Curr. Top Med. Chem. 2016, 16, 3385-3403.

[16]. Wickelgren, I. Science 1998, 281, 1264-1265.

[17]. Chauhan, A.; Mittal, A.; Arora, P. K. J. Pharm. Sci. Res. 2013, 4, 184-204.

[18]. Martinez, A.; Ibarra, I. A.; Vargas, R. PlosONE 2019, 14, e0224691.

[19]. Martinez, A.; Vargas, R. J. Pharm. Pharmaceut. Res. 2018, 1, 1-8.

[20]. Kiss, B.; Horvath, A.; Zs, N.; Schmidt, E.; Laszlovszky, I.; Gy, B.; Fazekas, K.; Hornok, K.; Sz, O.; Gyertyan, I.; Agai-Csongor, E.; Gy, D.; Tihanyi, K.; Adham, N.; Zs, S. J. Pharmacol. Exp. Ther. 2010, 333, 328-340.

[21]. Gyertyan, I.; Kiss, B.; Saghy, K.; Laszy, J.; Gy, S.; Szabados, T.; Gemesi, L. I.; Pasztor, G.; Zajer-Balazs, M.; Kapas, M.; Agai-Csongor, E.; Gy, D.; Tihanyi, K.; Zs, S. Neurochem. In. 2011, 59, 925-935.

[22]. McCormack, P. L. Drugs 2015, 75, 2035-2043.

[23]. Wager, T. T.; Chappie, T.; Horton, D.; Chandrasekaran, R. Y.; Samas, B.; Dunn-Sims, E. R.; Hsu, C.; Nawreen, N.; Vanase-Frawley, M. A.; O'Connor, R. E.; Schmidt, C. J.; Dlugolenski, K.; Stratman, N. C.; Majchrzak, M. J.; Kormos, B. L.; Nguyen, D. P.; Sawant-Basak, A.; Mead, A. N. ACS Chem. Neurosci. 2017, 8, 165-177.

[24]. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, Jr. , J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; P. Hratchian, H.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A., Gaussian 09, revision A. 02, Gaussian, Inc. , Wallingford CT, 2009.

[25]. Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215-241.

[26]. Petersson, G. A.; Bennett, A.; Tensfeldt, T. G.; Al-Laham, M. A.; Shirley, W. A. J. Chem. Phys. 1988, 89, 2193-2218.

[27]. Petersson, G. A.; Al-Laham, M. A. J. Chem. Phys. 1991, 94, 6081-6090.

[28]. McLean, A. D.; Chandler, G. S. J. Chem. Phys. 1980, 72, 5639-5648.

[29]. Raghavachari, K.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980, 72, 650-654.

[30]. Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B. 2009, 113, 6378-6396.

[31]. Islam, N.; Ghosh, D. C. Eur. J. Chem. 2010, 1, 83-89.

[32]. Islam, N. Eur. J. Chem. 2011, 2, 448-454.

[33]. Gazquez, J. L.; Cedillo, A.; Vela. A. J. Phys. Chem. A. 2007, 111, 1966-1970.

[34]. Gazquez, J. L. J. Mex. Chem. Soc. 2008, 52, 3-10.

[35]. Martinez, A.; Rodriguez-Girones, M. A.; Barbosa, A.; Costas, M. J. Phys. Chem. A. 2008, 112, 9037-9042.

[36]. Martinez, A. J. Phys. Chem. B. 2009, 113. 4915-4921.

[37]. Ceron-Carrasco, J. P.; Bastida, A.; Requena, A.; Zuniga, J.; Miguel, B. J. Phys. Chem. B. 2010, 114, 4366-4372.

[38]. Pillegowda, M.; Periyasamy, G. Comput. Theor. Chem. 2018, 1129, 26-36.

[39]. Alfaro, R. A. D.; Gomez-Sandoval, Z.; Mammino, L. J. Mol. Model. 2014, 20, 2337, 1-11.

[40]. Duarte, C.; Lefebvre, C.; Chaperon, F.; Hamon, M.; Thiébot, M. H. Neuropsychopharmacology 2003, 28, 1903-1915.

[41]. Maramai, S.; Gemma, S.; Brogi, S.; Campiani, G.; Butini, S.; Stark, H.; Brindisi, M. Front. Neurosci. 2016, 10, 1-13, Article 451.

[42]. Garcia-Ladona, F. J.; Cox. B. F. CNS Drug Rev. 2003, 9, 141-158.

[43]. Wicke, K.; Garcia-Ladona, J. Eur. J. Pharmacol. 2001, 424, 85-90.

[44]. Xi, Z. X.; Gardner, E. L. CNS Drug Rev. 2007, 13, 240-259.

How to cite

Martinez, A. Eur. J. Chem. 2020, 11(1), 84-90. doi:10.5155/eurjchem.11.1.84-90.1970
Martinez, A. Dopamine antagonists for the treatment of drug addiction: PF-4363467 and related compounds. Eur. J. Chem. 2020, 11(1), 84-90. doi:10.5155/eurjchem.11.1.84-90.1970
Martinez, A. (2020). Dopamine antagonists for the treatment of drug addiction: PF-4363467 and related compounds. European Journal of Chemistry, 11(1), 84-90. doi:10.5155/eurjchem.11.1.84-90.1970
Martinez, Ana. "Dopamine antagonists for the treatment of drug addiction: PF-4363467 and related compounds." European Journal of Chemistry [Online], 11.1 (2020): 84-90. Web. 3 Dec. 2022
Martinez, Ana. "Dopamine antagonists for the treatment of drug addiction: PF-4363467 and related compounds" European Journal of Chemistry [Online], Volume 11 Number 1 (31 March 2020)

The other citation formats (EndNote | Reference Manager | ProCite | BibTeX | RefWorks) for this article can be found online at: How to cite item

DOI Link:

CrossRef | Scilit | GrowKudos | Researchgate | Publons | ScienceGate | Scite | Lens | OUCI

WorldCat Paperbuzz | LibKey Citeas | Dimensions | Semanticscholar | Plumx | Kopernio | Zotero | Mendeley

ZoteroSave to Zotero MendeleySave to Mendeley

European Journal of Chemistry 2020, 11(1), 84-90 | doi: | Get rights and content


  • There are currently no refbacks.

Copyright (c) 2020 Authors

Creative Commons License
This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License ( By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License ( are administered by Atlanta Publishing House LLC (European Journal of Chemistry).

© Copyright 2010 - 2022  Atlanta Publishing House LLC All Right Reserved.

The opinions expressed in all articles published in European Journal of Chemistry are those of the specific author(s), and do not necessarily reflect the views of Atlanta Publishing House LLC, or European Journal of Chemistry, or any of its employees.

Copyright 2010-2022 Atlanta Publishing House LLC. All rights reserved. This site is owned and operated by Atlanta Publishing House LLC whose registered office is 2850 Smith Ridge Trce Peachtree Cor GA 30071-2636, USA. Registered in USA.