Diclofensine

Diclofensine
Clinical data
ATC code	None
Legal status
Legal status	Legal;
Identifiers
	IUPAC name 4-(3,4-dichlorophenyl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
CAS Number	67165-56-4
PubChem (CID)	68871
ChemSpider	62103
UNII	09HKW863J6
ChEMBL	CHEMBL287257
Chemical and physical data
Formula	C17H17Cl2NO
Molar mass	322.229 g/mol
3D model (Jmol)	Interactive image
	SMILES CN1CC(C2=C(C1)C=C(C=C2)OC)C3=CC(=C(C=C3)Cl)Cl ;
	InChI InChI=1S/C17H17Cl2NO/c1-20-9-12-7-13(21-2)4-5-14(12)15(10-20)11-3-6-16(18)17(19)8-11/h3-8,15H,9-10H2,1-2H3 ; Key:ZJDCGVDEEHWEIG-UHFFFAOYSA-N ;
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Diclofensine (Ro 8-4650) was developed by Hoffmann-La Roche in the 1970s^[1] in the search for a new antidepressant. It was found that the (S)-isomer was responsible for activity.^[2] Is a stimulant drug which acts as a triple monoamine reuptake inhibitor,^[3]^[4] primarily inhibiting the reuptake of dopamine^[5] and norepinephrine,^[6] with affinities (K_i) of 16.8 nM, 15.7 nM, and 51 nM for DAT, NET, and SERT (dopamine, norepinephrine and serotonin transporters), respectively.^[7] It was found to be an effective antidepressant in human trials,^[8]^[9]^[10] with relatively few side effects,^[11] but was ultimately dropped from clinical development, possibly due to concerns about its abuse potential.^[12]^[13]

Diclofensine is chemically a tetrahydroisoquinoline (THIQ) derivative, as is nomifensine.

References[edit]

^ US Patent 3947456 A, Alfred Rheiner, "Substituted 4-Phenyl Isoquinolines", published 1976-03-30, assigned to Hoffman-La Roche Inc.
^ Crossley, Roger (1995). Chirality and the Biological Activity of Drugs. 2000 Corporate Blvd., N.W., Boca Raton, Florida 33431: CRC Press, Inc. p. 138. ISBN 0-8493-9140-7. |access-date= requires |url= (help)
^ Keller, HH; Schaffner, R; Carruba, MO; Burkard, WP; Pieri, M; Bonetti, EP; Scherschlicht, R; Da Prada, M; Haefely, WE (1982). "Diclofensine (Ro 8-4650)—a Potent Inhibitor of Monoamine Uptake: Biochemical and Behavioural Effects in Comparison with Nomifensine". Advances in Biochemical Psychopharmacology. 31: 249–63. PMID 6979165. |access-date= requires |url= (help)
^ Omer, LM (July 1982). "Pilot Trials with Diclofensine, a New Psychoactive Drug in Depressed Patients". International Journal of Clinical Pharmacology, Therapy, and Toxicology. 20 (7): 320–6. PMID 7107085. |access-date= requires |url= (help)
^ Di Renzo, G; Amoroso, S; Taglialatela, M; Canzoniero, LM; Maida, P; Lombardi, G; Annunziato, L (1988). "Pure Uptake Blockers of Dopamine Can Reduce Prolactin Secretion: Studies with Diclofensine". Life Sciences. 42 (21): 2161–9. PMID 2968488. |access-date= requires |url= (help)
^ Gasić, S; Korn, A; Eichler, HG (May 1986). "Effect of Diclofensine, a Novel Antidepressant, on Peripheral Adrenergic Function". Clinical Pharmacology and Therapeutics. 39 (5): 582–5. doi:10.1038/clpt.1986.100. PMID 3698467. |access-date= requires |url= (help)
^ Andersen, PH (3 August 1989). "The Dopamine Inhibitor GBR 12909: Selectivity and Molecular Mechanism of Action". European Journal of Pharmacology. 166 (3): 493–504. PMID 2530094. |access-date= requires |url= (help)
^ Cherpillod, C; Omer, LM (1981). "A Controlled Trial with Diclofensine, a New Psychoactive Drug, in the Treatment of Depression". The Journal of International Medical Research. 9 (5): 324–9. PMID 7028532. |access-date= requires |url= (help)
^ Omer, OL; Díaz-Olivera, M; Ismail, S (March 1984). "Therapeutic Efficacy and Tolerance of Diclofensine in Psychoreactive Depression—a Double-Blind Comparison with Placebo". Methods and Findings in Experimental and Clinical Pharmacology. 6 (3): 147–51. PMID 6379345. |access-date= requires |url= (help)
^ Funke, HJ; Holtmann, W; Ismail, S; Jansen, W; Leonhardt, KF; Muth, H; Omer, LM; O'Connolly, M; Ramm, H (May 1986). "Double-Blind Comparison of Diclofensine with Nomifensine in Outpatients with Dysphoric Mood". Pharmacopsychiatry. 19 (3): 120–3. doi:10.1055/s-2007-1017168. PMID 3725890. |access-date= requires |url= (help)
^ Culig, J; Ehsanullah, RS; Hallett, C; Iliopoulou, A; Matheson, I; Turner, P (May 1983). "A Clinical Pharmacological Comparison of Diclofensine (Ro 8-4650) with Nomifensine and Amitriptyline in Normal Human Volunteers" (PDF). British Journal of Clinical Pharmacology. 15 (5): 537–43. doi:10.1111/j.1365-2125.1983.tb02087.x. PMC 1427714. PMID 6860528.
^ Lamb, RJ; Griffiths, RR (1990). "Self-Administration in Baboons and the Discriminative Stimulus Effects in Rats of Bupropion, Nomifensine, Diclofensine and Imipramine". Psychopharmacology. 102 (2): 183–90. PMID 2125734. |access-date= requires |url= (help)
^ Nakachi, N; Kiuchi, Y; Inagaki, M; Inazu, M; Yamazaki, Y; Oguchi, K (4 August 1995). "Effects of Various Dopamine Uptake Inhibitors on Striatal Extracellular Dopamine Levels and Behaviours in Rats". European Journal of Pharmacology. 281 (2): 195–203. PMID 7589207. |access-date= requires |url= (help)

[1] US Patent 3947456 A, Alfred Rheiner, "Substituted 4-Phenyl Isoquinolines", published 1976-03-30, assigned to Hoffman-La Roche Inc.

[2] Crossley, Roger (1995). Chirality and the Biological Activity of Drugs. 2000 Corporate Blvd., N.W., Boca Raton, Florida 33431: CRC Press, Inc. p. 138. ISBN 0-8493-9140-7. |access-date= requires |url= (help)

[3] Keller, HH; Schaffner, R; Carruba, MO; Burkard, WP; Pieri, M; Bonetti, EP; Scherschlicht, R; Da Prada, M; Haefely, WE (1982). "Diclofensine (Ro 8-4650)—a Potent Inhibitor of Monoamine Uptake: Biochemical and Behavioural Effects in Comparison with Nomifensine". Advances in Biochemical Psychopharmacology. 31: 249–63. PMID 6979165. |access-date= requires |url= (help)

[4] Omer, LM (July 1982). "Pilot Trials with Diclofensine, a New Psychoactive Drug in Depressed Patients". International Journal of Clinical Pharmacology, Therapy, and Toxicology. 20 (7): 320–6. PMID 7107085. |access-date= requires |url= (help)

[5] Di Renzo, G; Amoroso, S; Taglialatela, M; Canzoniero, LM; Maida, P; Lombardi, G; Annunziato, L (1988). "Pure Uptake Blockers of Dopamine Can Reduce Prolactin Secretion: Studies with Diclofensine". Life Sciences. 42 (21): 2161–9. PMID 2968488. |access-date= requires |url= (help)

[6] Gasić, S; Korn, A; Eichler, HG (May 1986). "Effect of Diclofensine, a Novel Antidepressant, on Peripheral Adrenergic Function". Clinical Pharmacology and Therapeutics. 39 (5): 582–5. doi:10.1038/clpt.1986.100. PMID 3698467. |access-date= requires |url= (help)

[7] Andersen, PH (3 August 1989). "The Dopamine Inhibitor GBR 12909: Selectivity and Molecular Mechanism of Action". European Journal of Pharmacology. 166 (3): 493–504. PMID 2530094. |access-date= requires |url= (help)

[8] Cherpillod, C; Omer, LM (1981). "A Controlled Trial with Diclofensine, a New Psychoactive Drug, in the Treatment of Depression". The Journal of International Medical Research. 9 (5): 324–9. PMID 7028532. |access-date= requires |url= (help)

[9] Omer, OL; Díaz-Olivera, M; Ismail, S (March 1984). "Therapeutic Efficacy and Tolerance of Diclofensine in Psychoreactive Depression—a Double-Blind Comparison with Placebo". Methods and Findings in Experimental and Clinical Pharmacology. 6 (3): 147–51. PMID 6379345. |access-date= requires |url= (help)

[10] Funke, HJ; Holtmann, W; Ismail, S; Jansen, W; Leonhardt, KF; Muth, H; Omer, LM; O'Connolly, M; Ramm, H (May 1986). "Double-Blind Comparison of Diclofensine with Nomifensine in Outpatients with Dysphoric Mood". Pharmacopsychiatry. 19 (3): 120–3. doi:10.1055/s-2007-1017168. PMID 3725890. |access-date= requires |url= (help)

[11] Culig, J; Ehsanullah, RS; Hallett, C; Iliopoulou, A; Matheson, I; Turner, P (May 1983). "A Clinical Pharmacological Comparison of Diclofensine (Ro 8-4650) with Nomifensine and Amitriptyline in Normal Human Volunteers" (PDF). British Journal of Clinical Pharmacology. 15 (5): 537–43. doi:10.1111/j.1365-2125.1983.tb02087.x. PMC 1427714. PMID 6860528.

[12] Lamb, RJ; Griffiths, RR (1990). "Self-Administration in Baboons and the Discriminative Stimulus Effects in Rats of Bupropion, Nomifensine, Diclofensine and Imipramine". Psychopharmacology. 102 (2): 183–90. PMID 2125734. |access-date= requires |url= (help)

[13] Nakachi, N; Kiuchi, Y; Inagaki, M; Inazu, M; Yamazaki, Y; Oguchi, K (4 August 1995). "Effects of Various Dopamine Uptake Inhibitors on Striatal Extracellular Dopamine Levels and Behaviours in Rats". European Journal of Pharmacology. 281 (2): 195–203. PMID 7589207. |access-date= requires |url= (help)

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Adamantanes	Adaphenoxate Adapromine Amantadine Bromantane Chlodantane Gludantane Memantine Rimantadine

Adenosine antagonists	8-Chlorotheophylline 8-Cyclopentyltheophylline 8-Phenyltheophylline Aminophylline Caffeine CGS-15943 Dimethazan Paraxanthine SCH-58261 Theobromine Theophylline

Alkylamines	Cyclopentamine Cypenamine Cyprodenate Heptaminol Isometheptene Levopropylhexedrine Methylhexaneamine Octodrine Propylhexedrine Tuaminoheptane

Ampakines	CX-516 CX-546 CX-614 CX-691 CX-717 IDRA-21 LY-404,187 LY-503,430 Nooglutyl Org 26576 PEPA S-18986 Sunifiram Unifiram

Arylcyclohexylamines	Benocyclidine Dieticyclidine Esketamine Eticyclidine Gacyclidine Ketamine Phencyclamine Phencyclidine Rolicyclidine Tenocyclidine Tiletamine

Benzazepines	6-Br-APB SKF-77434 SKF-81297 SKF-82958

Cholinergics	A-84,543 A-366,833 ABT-202 ABT-418 AR-R17779 Altinicline Anabasine Arecoline Bradanicline Cotinine Cytisine Dianicline Epibatidine Epiboxidine GTS-21 Ispronicline Nicotine PHA-543,613 PNU-120,596 PNU-282,987 Pozanicline Rivanicline Sazetidine A SIB-1553A SSR-180,711 TC-1698 TC-1827 TC-2216 Tebanicline UB-165 Varenicline WAY-317,538

Convulsants	Anatoxin-a Bicuculline DMCM Flurothyl Gabazine Pentetrazol Picrotoxin Strychnine Thujone

Eugeroics	Adrafinil Armodafinil CRL-40,940 CRL-40,941 Fluorenol JZ-IV-10 Modafinil

Oxazolines	4-Methylaminorex Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone

Phenethylamines	1-(4-Methylphenyl)-2-aminobutane 1-Phenyl-2-(piperidin-1-yl)pentan-3-one 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane 2-Fuoroamphetamine 2-Fuoromethamphetamine 2-OH-PEA 2-Phenyl-3-aminobutane 2-Phenyl-3-methylaminobutane 2,3-MDA 3-Fuoroamphetamine 3-Fluoroethamphetamine 3-Fluoromethcathinone 3-Methoxyamphetamine 3-Methylamphetamine 3,4-DMMC 4-BMC 4-CMC 4-Ethylamphetamine 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-MA 4-Methylbuphedrone 4-Methylcathinone 4-MMA 4-Methylpentedrone 4-MTA 6-FNE AL-1095 Alfetamine a-Ethylphenethylamine Amfecloral Amfepentorex Amfepramone Amidephrine 2-Amino-1,2-dihydronaphthalene 2-Aminoindane 5-(2-Aminopropyl)indole 2-Aminotetralin Acridorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Arbutamine β-Methylphenethylamine β-Phenylmethamphetamine Benfluorex Benzedrone Benzphetamine BDB BOH 3-Benzhydrylmorpholine BPAP Buphedrone Bupropion Butylone Camfetamine Cathine Cathinone Chlorphentermine Cilobamine Cinnamedrine Clenbuterol Clobenzorex Cloforex Clortermine Cypenamine D-Deprenyl Denopamine Dimethoxyamphetamine Dimethylamphetamine Dimethylcathinone Dobutamine DOPA (Dextrodopa, Levodopa) Dopamine Dopexamine Droxidopa EBDB Ephedrine Epinephrine Epinine Etafedrine Ethcathinone Ethylnorepinephrine Ethylone Etilamfetamine Etilefrine Famprofazone Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Feprosidnine Flephedrone Fludorex Formetorex Furfenorex Gepefrine Hexapradol Hexedrone HMMA Hordenine 4-Hydroxyamphetamine 5-Iodo-2-aminoindane Ibopamine IMP Indanylamphetamine Iofetamine Isoetarine Isoethcathinone Isoprenaline L-Deprenyl (Selegiline) Lefetamine Lisdexamfetamine Lophophine MBDB MDA MDBU MDEA MDMA MDMPEA MDOH MDPR MDPEA Mefenorex Mephedrone Mephentermine Metanephrine Metaraminol Mesocarb Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxamine Methoxyphenamine MMA Methcathinone Methedrone Methoxyphenamine Methylenedioxycathinone Methylone Mexedrone MMDA MMDMA MMMA Morforex N,alpha-Diethylphenylethylamine N-Benzyl-1-phenethylamine N-Ethylbuphedrone N-Ethylhexedrone N,N-Dimethylphenethylamine Naphthylamphetamine Nisoxetine Norepinephrine Norfenefrine Norfenfluramine Normetanephrine L-Norpseudoephedrine Octopamine (drug) Orciprenaline Ortetamine Oxifentorex Oxilofrine PBA PCA PCMA PHA Pentorex Pentedrone Pentylone Phenatine Phenpromethamine Phentermine Phenylalanine Phenylephrine Phenylpropanolamine Pholedrine PIA PMA PMEA PMMA PPAP Phthalimidopropiophenone Prenylamine Propylamphetamine Pseudoephedrine Ropinirole Salbutamol (Levosalbutamol) Sibutramine Synephrine Theodrenaline Tiflorex Tranylcypromine Tyramine Tyrosine Xylopropamine Zylofuramine

Phenylmorpholines	3-Fluorophenmetrazine Fenbutrazate Fenmetramide G-130 Manifaxine Morazone Morforex Oxaflozane PD-128,907 Phendimetrazine Phenmetrazine 2-Phenyl-3,6-dimethylmorpholine Pseudophenmetrazine Radafaxine

Piperazines	2C-B-BZP 3C-PEP BZP CM156 DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 GBR-13119 MeOPP MBZP Vanoxerine

Piperidines	1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine 1-(3,4-Dichlorophenyl)-1-(piperidin-2-yl)butane 2-Benzylpiperidine 2-Methyl-3-phenylpiperidine 3-Chloromethylphenidate 3,4-Dichloromethylphenidate 4-Benzylpiperidine 4-Fluoromethylphenidate 4-Methylmethylphenidate Desoxypipradrol Difemetorex Diphenylpyraline Ethylnaphthidate Ethylphenidate Methylnaphthidate Isopropylphenidate Methylphenidate (Dexmethylphenidate) N-Methyl-3β-propyl-4β-(4-chlorophenyl)piperidine Nocaine Phacetoperane Pipradrol Propylphenidate SCH-5472

Pyrrolidines	2-Diphenylmethylpyrrolidine 5-DBFPV α-PPP α-PBP α-PHP α-PVP α-PVT Diphenylprolinol DMPVP FPOP FPVP MDPPP MDPBP MPBP MPHP MPPP MOPVP MOPPP Indapyrophenidone MDPV Naphyrone PEP Picilorex Prolintane Pyrovalerone

Racetams	Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide

Tropanes	3-CPMT 3'-Chloro-3a-(diphenylmethoxy)tropane 4-fluorotropacocaine 4'-Fluorococaine AHN-1055 Altropane (IACFT) Brasofensine CFT (WIN 35,428) β-CIT (RTI-55) Cocaethylene Cocaine Dichloropane (RTI-111) Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (¹²³I) Norcocaine PIT PTT RTI-31 RTI-32 RTI-51 RTI-105 RTI-112 RTI-113 RTI-117 RTI-120 RTI-121 (IPCIT) RTI-126 RTI-150 RTI-154 RTI-171 RTI-177 RTI-183 RTI-193 RTI-194 RTI-199 RTI-202 RTI-204 RTI-229 RTI-241 RTI-336 RTI-354 RTI-371 RTI-386 Salicylmethylecgonine Tesofensine Troparil (β-CPT, WIN 35,065-2) Tropoxane WF-23 WF-33 WF-60

Tryptamines	4-HO-αMT 4-Methyl-αET 4-Methyl-αMT 5-Chloro-αMT 5-Fluoro-αMT 5-MeO-αET 5-MeO-αMT 5-MeO-DIPT 6-Fluoro-αMT 7-Methyl-αET αET αMT

Others	2-MDP 2-Phenylcyclohexylamine 3,3-Diphenylcyclobutanamine Amfonelic acid Amineptine Amiphenazole Atipamezole Atomoxetine Bemegride Benzydamine BTQ BTS 74,398 Centanafadine Ciclazindol Clofenciclan Cropropamide Crotetamide D-161 Diclofensine Dimethocaine Efaroxan Etamivan Fenisorex Fenpentadiol Gamfexine Gilutensin GSK1360707F GYKI-52895 Hexacyclonate Idazoxan Indanorex Indatraline JNJ-7925476 Lazabemide Leptacline Lomevactone LR-5182 Mazindol Meclofenoxate Medifoxamine Mefexamide Methamnetamine Methastyridone Methiopropamine Naphthylaminopropane Nefopam Nikethamide Nomifensine O-2172 Oxaprotiline PNU-99,194 PRC200-SS Rasagiline Rauwolscine Rubidium chloride Setazindol Tametraline Tandamine Thiopropamine Thiothinone Trazium UH-232 Yohimbine

ATC code: N06B

Diclofensine

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