PR-000608

{{Short description|Dopamine reuptake inhibitor}}

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{{Infobox drug

| drug_name = PR-608

| image = PR-608.svg

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| CAS_number = 143759-63-1

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| PubChem = 3072701

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| ChemSpiderID = 2332014

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| synonyms = PR 000608

| IUPAC_name = 1-(4,4-Bis(4-fluorophenyl)butyl)-4-(2-hydroxy-3-phenylaminopropyl)piperazine

| C=29 | H=35 | F=2 | N=3

| SMILES = C1CN(CCN1CCCC(C2=CC=C(C=C2)F)C3=CC=C(C=C3)F)CC(CNC4=CC=CC=C4)O

| StdInChI =1S/C29H35F2N3O/c30-25-12-8-23(9-13-25)29(24-10-14-26(31)15-11-24)7-4-16-33-17-19-34(20-18-33)22-28(35)21-32-27-5-2-1-3-6-27/h1-3,5-6,8-15,28-29,32,35H,4,7,16-22H2

| StdInChIKey = YIBOKAQCZWKXIM-UHFFFAOYSA-N

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PR-608 is a potent dopamine reuptake inhibitor of the 4,4-diphenylbutylpiperazine class, structurally related to vanoxerine. Other members of this class include amperozide and lidoflazine. A related stimulant is difluanazine.{{cite web | url = https://pubchem.ncbi.nlm.nih.gov/compound/21693 | title = Difluanazine | work = PubChem | publisher = U.S. National Library of Medicine }}{{cite patent | country = US | number = 3267104 | title = 1,4-Disubstituted piperazines and diazepines | inventor = Hermans HK, Karl-Adolf SW | assign = Janssen Pharmaceutica NV | gdate = 16 August 1966 | url = https://patents.google.com/patent/US3267104A/en?oq=US+3267104 }}

It has been shown in preclinical studies to inhibit dopamine uptake in the central nervous system and may have potential applications in neuropsychiatric and cardiovascular disorders.{{cite journal | vauthors = Kimura M, Masuda T, Yamada K, Mitani M, Kubota N, Kawakatsu N, Kishii K, Inazu M, Kiuchi Y, Oguchi K, Namiki T | title = Syntheses of novel diphenyl piperazine derivatives and their activities as inhibitors of dopamine uptake in the central nervous system | journal = Bioorganic & Medicinal Chemistry | volume = 11 | issue = 8 | pages = 1621–1630 | date = April 2003 | pmid = 12659747 | doi = 10.1016/s0968-0896(03)00061-0 }}{{cite journal | vauthors = Kimura M, Masuda T, Yamada K, Mitani M, Kubota N, Kawakatsu N, Kishii K, Inazu M, Kiuchi Y, Oguchi K, Namiki T | title = Novel diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter | journal = Bioorganic & Medicinal Chemistry | volume = 11 | issue = 18 | pages = 3953–3963 | date = September 2003 | pmid = 12927856 | doi = 10.1016/s0968-0896(03)00428-0 }}{{cite journal | vauthors = Kimura M, Masuda T, Yamada K, Mitani M, Kubota N, Kawakatsu N, Kishii K, Inazu M, Kiuchi Y, Oguchi K, Namiki T | title = Efficient asymmetric syntheses, determination of absolute configurations and biological activities of 1-[4,4-bis(4-fluorophenyl)butyl]-4-[2-hydroxy-3-(phenylamino)propyl]piperazine as a novel potent dopamine uptake inhibitor in the central nervous system | journal = Bioorganic & Medicinal Chemistry | volume = 12 | issue = 11 | pages = 3069–3078 | date = June 2004 | pmid = 15142566 | doi = 10.1016/j.bmc.2004.02.041 }}{{cite patent | title = Diphenylpiperazine derivative and drug for circulatory organ containing the same. | country = US | number = 5391552 | inventor = Inazu M, Miyata Y, Morimoto T, Yamamoto T, Yoshiko Y, Harada K, Momota Y, Yanagi M, Yokota R, Katoh T, Namiki T, Kimura M, Kawakatsu N | assign = Pola Orbis Holdings Inc. | gdate = 21 February 1995 | url = https://patents.google.com/patent/US5391552A/en?oq=US5391552 }}

The calcium channel blocking properties of PR-608 might make it useful as a cardiac stimulant for the treatment of heart disease or as a cerebral vasodilator.{{cite journal | vauthors = Kimura M, Masuda T, Yamada K, Kubota N, Kawakatsu N, Mitani M, Kishii K, Inazu M, Namiki T | title = Novel diphenylalkyl piperazine derivatives with dual calcium antagonistic and antioxidative activities | journal = Bioorganic & Medicinal Chemistry Letters | volume = 12 | issue = 15 | pages = 1947–1950 | date = August 2002 | pmid = 12113815 | doi = 10.1016/s0960-894x(02)00322-0 }} Alternative applications of this agent include for the treatment of psychostimulant addiction, neurodegenerative diseases including (but not limited to) Parkinson's disease,{{cite web | title = PR-000608 | url = https://synapse.patsnap.com/drug/d8b30286a81649f4882c3a6f88dfb09f | work = PatSnap }}{{cite journal | vauthors = Harada M, Kubota N, Masuda T, Inazu M | title = P-525: Effects of PR-000608, a novel antiparkinson drug, on MPTP-induced parkinsonism. | journal = Japanese Journal of Pharmacology | volume = 71 | date = January 1996 | doi = 10.1016/S0021-5198(19)36998-7 | page = 190 | url = https://www.researchgate.net/publication/347015032 }} and as a treatment for depression.{{cn|date=April 2025}}