NLS-3 (Levophacetoperane or (R,R) Phacetoperane): A Reverse Ester of Methylphenidate: A Literature Review


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Background: NLS-3 or (R, R) enantiomer of phacetoperane (levophacetoperane) is the reverse ester of methylphenidate, a well-documented psychostimulant marketed for the treatment of attention-deficit/hyperactivity disorder (ADHD) since the end of 1950s. Launched in Canada and Europe by Specia Rhône-Poulenc and Rhodia, marketed as Lidepran® (8228 R.P.), for the treatment of obesity and depression, phacetoperane became an increasingly popular psychiatric medication from 1959 to 1967. Previous data supported that the stimulant effect of phacetoperane differed from those of other medications acting on the catecholamine system (e.g., methylphenidate, amphetamine), with an advantage of benefit/risk balance. Method: The goal of this study is to characterize the binding profile of NLS-3 using in vitro and in vivo assays and hypothesize potential therapeutic uses considering all available data. Results: A complete binding profile assay confirmed the potential benefit of phacetoperane with a higher benefit/risk compared to other stimulants. NLS-3 synthesis resulted from phenylketone, which is also used for the synthesis of methylphenidate. It differs from that used by Rhône-Poulenc SA laboratories, allowing the possibility of individualizing several enantiomers not synthesized previously. The present review also confirmed extensive clinical use of the compound in almost one thousand children and adolescents in large dose ranges with fewer side effects versus comparative treatments. Furthermore, levophacetoperane was found to be generally well-tolerated by the subjects. Conclusion: NLS-3 could be a safer and more potent alternative to stimulants for patients with ADHD.

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Eric Konofal

Centre Pédiatrique des Pathologies du Sommeil, APHP Hôpital Robert Debré

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Michel Lecendreux

Centre Pédiatrique des Pathologies du Sommeil, APHP Hôpital Robert Debré

Email: info@benthamscience.net

Jean-Charles Bizot

, Key-Obs SAS

Email: info@benthamscience.net

Anh-Tuan Lormier

Department of ChemistryCAYLAB,, 2 Chemin de la Romaniquette

Email: info@benthamscience.net

Bruno Figadère

BioCIS, Faculté de Pharmacie,, Université Paris-Saclay

编辑信件的主要联系方式.
Email: info@benthamscience.net

参考

  1. Bradley, C. The behavior of children receiving benzedrine. Am. J. Psychiatry, 1937, 94(3), 577-585. doi: 10.1176/ajp.94.3.577
  2. Cortese, S.; Adamo, N.; Del Giovane, C.; Mohr-Jensen, C.; Hayes, A.J.; Carucci, S.; Atkinson, L.Z.; Tessari, L.; Banaschewski, T.; Coghill, D.; Hollis, C.; Simonoff, E.; Zuddas, A.; Barbui, C.; Purgato, M.; Steinhausen, H.C.; Shokraneh, F.; Xia, J.; Cipriani, A. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry, 2018, 5(9), 727-738. doi: 10.1016/S2215-0366(18)30269-4 PMID: 30097390
  3. Wigal, T.L.; Newcorn, J.H.; Handal, N.; Wigal, S.B.; Mulligan, I.; Schmith, V.; Konofal, E. a double-blind, placebo- controlled, phase ii study to determine the efficacy, safety, tolerability and pharmacokinetics of a controlled release (CR) formulation of mazindol in adults with DSM-5 attention-deficit/hyperactivity disorder (ADHD). CNS Drugs, 2018, 32(3), 289-301. doi: 10.1007/s40263-018-0503-y PMID: 29557078
  4. Nageye, F.; Cortese, S. Beyond stimulants: A systematic review of randomised controlled trials assessing novel compounds for ADHD. Expert Rev. Neurother., 2019, 19(7), 707-717. doi: 10.1080/14737175.2019.1628640 PMID: 31167583
  5. Polanczyk, G.; de Lima, M.S.; Horta, B.L.; Biederman, J.; Rohde, L.A. The worldwide prevalence of ADHD: A systematic review and metaregression analysis. Am. J. Psychiatry, 2007, 164(6), 942-948. doi: 10.1176/ajp.2007.164.6.942 PMID: 17541055
  6. Posner, J.; Polanczyk, G.V.; Sonuga-Barke, E. Attention-deficit hyperactivity disorder. Lancet, 2020, 395(10222), 450-462. doi: 10.1016/S0140-6736(19)33004-1 PMID: 31982036
  7. Thorpy, M.J.; Hiller, G. The medical and economic burden of narcolepsy: Implications for managed care. Am. Health Drug Benefits, 2017, 10(5), 233-241. PMID: 28975007
  8. Konofal, É.; Dolitsky, D. ADHD andits medications, an illustrated history over time. Impulsion naturelle, 2019. Available from: http://impulsion-naturelle.fr/produit/ adhd-its-medications-an-illustrated-history-over/
  9. Morton, W.A.; Stock, G.G. methylphenidate abuse and psychiatric side effects. Prim. Care Companion J. Clin. Psychiatry, 2000, 2(5), 159-164. doi: 10.4088/PCC.v02n0502 PMID: 15014637
  10. Conners, C.K.; Eisenberg, L. The effects of methylphenidate on symptomatology and learning in disturbed children. Am. J. Psychiatry, 1963, 120(5), 458-464. doi: 10.1176/ajp.120.5.458 PMID: 14051237
  11. Cortese, S.; Holtmann, M.; Banaschewski, T.; Buitelaar, J.; Coghill, D.; Danckaerts, M.; Dittmann, R.W.; Graham, J.; Taylor, E.; Sergeant, J. Practitioner Review: Current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents. J. Child Psychol. Psychiatry, 2013, 54(3), 227-246. doi: 10.1111/jcpp.12036 PMID: 23294014
  12. Sivadon, P. Chanoit; Azoulay. First clinical results of the use of a new psycho-tonic. The 8228 R.P. Ann. Med. Psychol. (Paris), 1959, II, 536-537. PMID: 13854835
  13. Konofal, E.; Figadere, B. Phacetoperane to treat attention deficit hyperactivity disorder. EP Patents EP2785344B1, 2016.
  14. Thai, D.L.; Sapko, M.T.; Reiter, C.T.; Bierer, D.E.; Perel, J.M. Asymmetric synthesis and pharmacology of methylphenidate and its para-substituted derivatives. J. Med. Chem., 1998, 41(4), 591-601. doi: 10.1021/jm970620j PMID: 9484508
  15. Nahm, S.; Weinreb, S.M. N-methoxy-n-methylamides as effective acylating agents. Tetrahedron Lett., 1981, 22(39), 3815-3818. doi: 10.1016/S0040-4039(01)91316-4
  16. Dargazanli, G.; Estienne-Bouhtou, G.; Marabout, B.; Roger, P.; Sevrin, M. N-phenyl(piperidin-2-Yl)methylbenzamide derivatives, preparation thereof, and use thereof in therapy. EP Patent EP1527048A2, 2005.
  17. Dewar, G.H.; Parfitt, R.T.; Sheh, L. Stereochemical features of reduction and elimination reactions of 8-emthyl-6-phenyl-8-azabicyclo(3.2.1)oct-6-ene (6-phenyl-6-tropene). Chem. Informationsd., 1985, 1, 16.
  18. Pham, V.C.; Charlton, J.L. Methyl (S)-Lactate as a chiral auxiliary in the asymmetric synthesis of Bao Gong Teng A. J. Org. Chem., 1995, 60(24), 8051-8055. doi: 10.1021/jo00129a053
  19. Laboratoires specia. Lidepran: Psychoactive lidepran; Paris, 1963.
  20. Ziolko, H.U. The significance of psychodynamic factors for the effect of phenylpiperidylcarbinol (Bayer 1313). Med. Exp. Int. J. Exp. Med., 1960, 2, 224-227. PMID: 13847609
  21. Michel, J.R.; Marie, J.N. New esters. US Patent US2928835A, 1960.
  22. Ramirez, A.; Vial, H.; Barailler, J.; Pacheco, H. Effects of levophacetoperane, pemoline, fenozolone, and centrophenoxine on catecholamines and serotonin uptake in various parts of the rat brain. C.R. Acad. Hebd. Seances Acad. Sci. D, 1978, 187(1), 53-56. PMID: 29714
  23. Snyder, S.H.; Coyle, J.T. Regional differences in H3-norepinephrine and H3-dopamine uptake into rat brain homogenates. J. Pharmacol. Exp. Ther., 1969, 165(1), 78-86. PMID: 5782836
  24. Hanna, C.; Upton, P.D.; Chambers, W.F. Comparative effects of D-1 amphetamine and 1-phenyl-1-(piperidyl-2′)-1-acetoxy-1-methane (R.P. 8228) in antagonizing barbiturate hypnosis. Arch. Int. Pharmacodyn. Ther., 1963, 145, 553-564. PMID: 14067576
  25. Yung-Chi, C.; Prusoff, W.H. Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol., 1973, 22(23), 3099-3108. doi: 10.1016/0006-2952(73)90196-2 PMID: 4202581
  26. Zlotos, D.P.; Bender, W.; Holzgrabe, U. Muscarinic receptor agonists and antagonists. Expert Opin. Ther. Pat., 1999, 9(8), 1029-1053. doi: 10.1517/13543776.9.8.1029
  27. Schenk, S.; Partridge, B. Sensitization to cocaine’s reinforcing effects produced by various cocaine pretreatment regimens in rats. Pharmacol. Biochem. Behav., 2000, 66(4), 765-770. doi: 10.1016/S0091-3057(00)00273-2 PMID: 10973514
  28. Schenk, S.; Shippenberg, T.S.; Partridge, B. U69593, a kappa-opioid agonist, decreases cocaine self-administration and decreases cocaine-produced drug-seeking. Psychopharmacology (Berl.), 1999, 144(4), 339-346. doi: 10.1007/s002130051016 PMID: 10435406
  29. Schenk, S.; Partridge, B.; Shippenberg, T.S. Reinstatement of extinguished drug-taking behavior in rats: Effect of the kappa-opioid receptor agonist, U69593. Psychopharmacology (Berl.), 2000, 151(1), 85-90. doi: 10.1007/s002130000476 PMID: 10958121
  30. Schenk, S.; Partridge, B. Cocaine-seeking produced by experimenter-administered drug injections: dose-effect relationships in rats. Psychopharmacology (Berl.), 1999, 147(3), 285-290. doi: 10.1007/s002130051169 PMID: 10639687
  31. Morani, A.S.; Kivell, B.; Prisinzano, T.E.; Schenk, S. Effect of kappa-opioid receptor agonists U69593, U50488H, spiradoline and salvinorin A on cocaine-induced drug-seeking in rats. Pharmacol. Biochem. Behav., 2009, 94(2), 244-249. doi: 10.1016/j.pbb.2009.09.002 PMID: 19747933
  32. Spangler, R.; Zhou, Y.; Maggos, C.E.; Schlussman, S.D.; Ho, A.; Kreek, M.J. Prodynorphin, proenkephalin and κ opioid receptor mRNA responses to acute "binge" cocaine. Brain Res. Mol. Brain Res., 1997, 44(1), 139-142. doi: 10.1016/S0169-328X(96)00249-5 PMID: 9030708
  33. Wee, S.; Koob, G.F. The role of the dynorphin–κ opioid system in the reinforcing effects of drugs of abuse. Psychopharmacology (Berl.), 2010, 210(2), 121-135. doi: 10.1007/s00213-010-1825-8 PMID: 20352414
  34. Groer, C.E.; Tidgewell, K.; Moyer, R.A.; Harding, W.W.; Rothman, R.B.; Prisinzano, T.E.; Bohn, L.M. An opioid agonist that does not induce mu-opioid receptor-arrestin interactions or receptor internalization. Mol. Pharmacol., 2007, 71(2), 549-557. doi: 10.1124/mol.106.028258 PMID: 17090705
  35. Kivell, B.M.; Ewald, A.W.M.; Prisinzano, T.E.; Salvinorin, A. Salvinorin A analogs and other κ-opioid receptor compounds as treatments for cocaine abuse. Adv. Pharmacol., 2014, 69, 481-511. doi: 10.1016/B978-0-12-420118-7.00012-3 PMID: 24484985
  36. Simonson, B.; Morani, A.S.; Ewald, A.W.M.; Walker, L.; Kumar, N.; Simpson, D.; Miller, J.H.; Prisinzano, T.E.; Kivell, B.M. Pharmacology and anti-addiction effects of the novel κ opioid receptor agonist Mesyl Sal B, a potent and long-acting analogue of salvinorin A. Br. J. Pharmacol., 2015, 172(2), 515-531. doi: 10.1111/bph.12692 PMID: 24641310
  37. Butelman, E.R.; Kreek, M.J. Discriminative stimulus properties of opioid ligands: Progress and future directions. Curr. Top. Behav. Neurosci., 2016, 39, 175-192. doi: 10.1007/7854_2016_9 PMID: 27225498
  38. Courvoisier, S. Étude des propriétés stimulantes centrales de l’acétoxy-l-phényl-l(pipéridyl-2′)-l-méthane, threo, levogyre (8228 R. P.). Ann. Med. Psychol. (Paris), 1959, 117, 345.
  39. Fournier Michel. Contribution to the study of the effects of lidepran. In: Neuro-Psychiatrie Infantile; Faculty of Medicine of Paris: Paris, 1962.
  40. Dobkin, A.B. Drugs which stimulate affective behavior. 2. Comparison of the analeptic effect of d’amphetamine, bemigride with amiphenazole, methylphenidylacetate, iproniazid (micoren) and RP8228. Anaesthesia, 1960, 15, 146-153. doi: 10.1111/j.1365-2044.1960.tb13319.x PMID: 13817063
  41. Bontronc, C.; Médecine, U. de P. About the psychotonics levophacetoperan and methylphenidate. The Psychoses and in Minor Psychoneurotic States; R. Vezin, 1961.
  42. Salinger, R.J. Contribution to the experimental study of new psychoactive medications and their therapeutic use in psychiatry: about one of them: 8228 RP or phenyl-1 (piperidyl-2’) 1-acetoxy-methane threolevogyre hydrochloride. 1961.
  43. Jean-Charles, B.; Trovero, F.; Figadere, B.; Akagah, B.; Konofal, E. Examination of potential addictive effects of NLS-3, a new compound in development for ADHD. 4th International Conference on ADHD, 16th-19th OctoberBerlin, Germany, 2016.
  44. Sivadon, P.; Salinger, R.J.; Quidu, M. Clinical results of the use in psychiatry of a new psychotonic: the 8228 RP (about the first 134 observations). Reports of the Meetings of the Academy of Sciences (Paris), 1960, 760-769.
  45. Sivadon, P. Salinger René. Ann. Med. Psychol. (Paris), 1962, 120, 824-832. PMID: 13913515
  46. Chanoit, P-F. Some considerations about the psychotherapeutic use of a new psychotonic. Ann. Med. Psychol. (Paris), 1960, 118, 869-878. PMID: 13692358
  47. Follin, S.; Chanoit, P-F.; Huchon, J. The use of a new psychotonic: The 8228 RP. In a hospital environment (assessment performed after two years of trials). Reports Meet. Acad. Sci., 1970, 770-776.
  48. Guyotat, J.; Hochmann, J. The present status of RP-8228 in psychiatric therapeutics. Apropos of 32 recent cases. Lyon Med., 1962, 94, 777-783. PMID: 13951512
  49. Labaï, C. Clinical results and remarks drawn from the use of iproniazid, RP 82-28 and nialamide in a departmental psychiatric hospital setting; Print South West: Toulouse, 1961.
  50. Oules, J.; Labaï, C. Therapeutic. Free Subjects: Indications and Use of a New Psychotonic: The 8228 RP. In: Proceedings of the Congress of Psychiatry and Neurology in the French Language Lille, 1960.
  51. Garde, A. Results obtained with 8.228 R.P. after two years of use of this psychotonic. Lyon Med., 1962, 94, 1549-1555. PMID: 13896864
  52. Deshaies, G.; Fontaine, C.; Spelz, M.T. Use of a psychotonic in psychiatry. Ann. Med. Psychol. (Paris), 1965, 123, 630-637. PMID: 14296669
  53. Grimberg, L.; Grimberg-Pivet, S. Psychiatry. Therapeutic. Intervention: Thoughts on the clinical use of 8228 RP. Or levophacetoperane (Lidepran). Proc. Congr. Psychiatry Neurol. French Lang., 1965, 1, p. 812.
  54. Faure, H.; Faure, M.L. Les Apports Du Nozinan. Neuro-Psychiatrie Infantile (Levomépromazine, 70.44. RP.). Psychological and Sociological Problems in Imbecility; Karger Publishers: Switzerland ; , 1963, pp. 160-164.
  55. Beaujard, M.; Revol, E. Clinical tests of the activity of RP 8228 (phacetoperane) in an oligophrenic child. Pediatrie, 1960, 15, 310-316. PMID: 13797965
  56. Guyotat, J.; Beaujard, M.; Guillaumin, J. Psychometric Evaluation of the Effects of a Psychotonic, 8.228R.P. Methodological Considerations. Communication to the Neuro-Psychopharmacological College, Basel, July 4-7, 1960. Neuropharmacology, 1961, 2, 361-370.
  57. Beaujard, M. Phacetoperane in Mental Retardation of Children. In: International Congress Series; Experta Medica, 1960; p. 100.
  58. Bellander-Löfvenberg, S.; Osterman, E.; Brattemo, C.E. R P - 8228-Ett nytt psykoanalepticum. Nord. Psykiatr. Tidsskr., 1961, 15(2), 141-147. doi: 10.3109/08039486109167941
  59. Penteado Bueno, U.; Capp, A.B. Clinical results (consequent to the use of a new psychotonic in oligophrenic and epileptic and oligophrenic minors. Hospital Rio J., 1962, 62, 1003-1017.
  60. Sivadon, P.; Chanoit, P.-F.; Azoulay, J. First clinical results with a new psychotonic, RP 8228. Méd. Psychol., 1959, 117, 536-541.
  61. Ban, T.A.; St Laurent, J. The stimulating effect of RP 8228 on inactive psychiatric patients. J. Nutr., 1961, 3, 91-95. PMID: 13864565
  62. Brattemo, C.E. Experimentalpsykologisk undersökning med ett psykotonicum, RP. - 8228. Nord. Psykiatr. Tidsskr., 1961, 15(2), 147-154. doi: 10.3109/08039486109167942
  63. Leitch, A.; Seager, C.P. A trial of four anti-depressant drugs. Psychopharmacology (Berl.), 1963, 4(1), 72-77. doi: 10.1007/BF00429366 PMID: 14050414
  64. Devic, M.; Revol, M.; Michel, F. Apropos of the treatment of narcolepsy: trial use of a new psychoactive agent, R.P. 8228. Lyon Med., 1962, 94, 1557-1562. PMID: 13885883
  65. Joncev, V.; Stefanova, E. Investigations on levophacetoperan effect upon higher nervous activity and memory. Folia Med. (Plovdiv), 1967, 9(6), 368-372. PMID: 4972459
  66. Beaujard, M. Phacetoperan in mental retardation in children. , 1963; pp. 165-167.
  67. Faure, H.; Faure, M.L.; Stoppa, I. The activating effects of phacetoperan in childhood neuropsychiatry. J. Child Neuropediatrics Childhood Mental Hygiene, 1962, 10, 7-8.
  68. Cutler, M.; Little, J.; Strauss, A. The effect of benzedrine on mentally deficient children. Am. J. Ment. Defic., 1940, 45, 59-65.
  69. Morris, J.V.; Macgillivray, R.C.; Mathieson, C.M. The results of the experimental administration of amphetamine sulphate in oligophrenia. J. Ment. Sci., 1955, 101(422), 131-140. doi: 10.1192/bjp.101.422.131 PMID: 14368214
  70. Raymond, F.; Janet, P. Review of les obsessions et la psychasthénie. Am. J. Psychol.,1903, 14(2), 262-264. doi: 10.2307/1412725
  71. Pitman, R.K. Janet’sObsessions and psychasthenia: A synopsis. Psychiatr. Q., 1984, 56(4), 291-314. doi: 10.1007/BF01064475 PMID: 6399751
  72. Hubin, P.; Servais, J. study of the subjective effects of amphtamine in humans according to personality. Psychopharmacology (Berl.), 1968, 12(3), 239-249. doi: 10.1007/BF00403778
  73. Sutter, J.M.; Delpretti, G.M. Levophacetoperane (lidepran) in psychiatric therapeutics. Sud Med. Chir., 1962, 998-1005.
  74. Fluyau, D.; Mitra, P.; Lorthe, K. Antipsychotics for amphetamine psychosis. A systematic review. Front. Psychiatry, 2019, 10, 740. doi: 10.3389/fpsyt.2019.00740 PMID: 31681046
  75. Doyle, J.B.; Daniels, L.E. Narcolepsy; Results of treatment with ephedrine sulphate. J. Am. Med. Assoc., 1932, 98(7), 542-545. doi: 10.1001/jama.1932.02730330024006
  76. Yoss, R.E.; Daly, D. Treatment of narcolepsy with Ritalin. Neurology, 1959, 9(3), 171-173. doi: 10.1212/WNL.9.3.171 PMID: 13632876
  77. Janota, O. Treatment of Narcolepsy With Ephedrine. Proceedings of the Proceedings of the work of the Neuro-Psychiatric Section of the 14th Congress of Polish Physicians and Naturalists, Poznan, 1933.
  78. Mondenard, J. Doping: Piperidines: Lidépran, Mératran, Ritalin. Odds and ends without great effects. Médecine du sport, 1991, 65, 00145-00148.
  79. Delbeke, F.T.; Debackere, M. Isolation and detection of methylphenidate, phacetoperane and some other sympatomimetic central nervous stimulants with special reference to doping. J. Chromatogr. A, 1975, 106(2), 412-417. doi: 10.1016/S0021-9673(00)93853-6 PMID: 239015

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