Diclofensine

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 (Ki) 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
Clinical data
ATC code
  • None
Legal status
Legal status
  • In general: legal
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC17H17Cl2NO
Molar mass322.229 g/mol g·mol−1
3D model (JSmol)
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Diclofensine is chemically a tetrahydroisoquinoline (THIQ) derivative, as is nomifensine.

See also

References
  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 978-0-8493-9140-8.
  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.
  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.
  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. doi:10.1016/0024-3205(88)90131-2. PMID 2968488.
  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.
  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. doi:10.1016/0014-2999(89)90363-4. PMID 2530094.
  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. doi:10.1177/030006058100900505. PMID 7028532.
  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.
  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.
  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". 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. doi:10.1007/bf02245920. PMID 2125734.
  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. doi:10.1016/0014-2999(95)00246-h. PMID 7589207.
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