Skip to main content
SpringerLink
Log in

First-Generation Antipsychotics as a Bridge to Second-Generation Antipsychotics in the Japanese Pharmaceutical Industry: Mosapramine, Timiperone, Zotepine, and Nemonapride

  • Living reference work entry
  • First Online:
NeuroPsychopharmacotherapy

  • 27 Accesses

Abstract

The introduction of antipsychotics into Japan began with chlorpromazine in 1955. Haloperidol was introduced in 1964, and several butyrophenone antipsychotics, benzamides. In 1961, carpipramine was first synthesized as the world’s first iminodibenzyl antipsychotic drug with a strong consciousness that Japan should develop its own antipsychotic drug, followed by clocapramine and mosapramine as improved versions. Furthermore, zotepine, the dibenzothiazepine-based antipsychotic, was synthesized in 1981. In 1973, the butyrophenone-based timiperone and, in 1978, the benzamide-based nemonapride were synthesized. Both were successfully marketed on the basis of clinical trials, and they have been widely used. Some of them, such as zotepine, were unique antipsychotics that were later classified as atypical antipsychotics. In this chapter, we describe the substance entry of four antipsychotics developed in Japan (mosapramine, timiperone, zotepine, and nemonapride).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Fukuda T, Setoguchi M, Morimoto Y, Shoji H, Tumagari T, Maruyama Y. Neuroleptic properties of Y-516, a new iminodibenzyl derivative. Folia Pharmacol Jpn. 1985;86:197–208.

    Article  CAS  Google Scholar 

  • Harada T. From the discovery of antimanic effect to the recent positioning as a novel atypical neuroleptic. Jpn J Clin Psychopharmacol. 1998;1:1187–93. (in Japanese, Abstract in English).

    Google Scholar 

  • Imai H, Nakamura M, Hukui Y, Tanaka K, Mori M, Hukui K, et al. Comparison of efficacy of zotepine and perphenazine in schizophrenia by double-blind, controlled study. Jpn J Neuropsychopharmacol. 1980;2:285–99. (in Japanese, Abstract in English).

    Google Scholar 

  • Inanaga K, Nakamura J, Takahashi R, Ootsuki SM, Samejima K, Sarai K, et al. Comparison of anti-manic efficacy of timiperone injection and haloperidol injection by double-blind controlled study. J Clin Med. 1985;1:1329–44. (in Japanese, Abstract in English).

    Google Scholar 

  • Iwanaga M, Akazawa S, Abe T, Arai H, Ando K, Ichimiya H, et al. Clinical evaluation of zotepine in chronic schizophrenia – a multi-institutional double-blind study in comparison with propericiazine. Jpn J Clin Psychiatry. 1980;9:873–91. (in Japanese).

    Google Scholar 

  • Iwanami S, Takahashi M, Hirata Y, Usuda S. Synthesis and neuroleptic activity of benzamides, cis-N-(1-benzyl-2-methylpyrrolidine-3-yl)-5-chloro-2- methoxy-4-(methylamine) benzamide and related compounds. J Med Chem. 1984;24:1224–30.

    Article  Google Scholar 

  • Kanno K, Shimazono Y, Tooru M, Mori A, Kariya T, Murasaki M, et al. Clinical usefulness of timiperome injection (DD-3480) for schizophrenia -double-blind multi-center comparative study with haloperidol injection. J Clin Med. 1985;1:1311–28. (in Japanese, Abstract in English).

    Google Scholar 

  • Kariya T, Shimazono Y, Yamasita I, Kanno K, Tooru M, Moar A, Murasaki M, Itoh S. Comparison of clinical effects of timiperone and haloperidol on schizophrenia using double-blind technique. J Clin Psychiatry. 1981;10:1281–301, (in Japanese).

    Google Scholar 

  • Kato N, Takahashi R, Yagi G, Kazamatsuri H, Mori A, Murasaki M. A double-blind comparison of a new iminodibenzyl compound Y-516 with clocapramine in the pharmacotherapy of schizophrenia. Clin Eval. 1989;17:177–96. (in Japanese, Abstract in English).

    Google Scholar 

  • Kudo Y, Ikawa G, Kawakita Y, Saito M, Sakai T, Nakajima T, Nishimura K, Higasi Y, Hitomi K. A double-blind comparative study of a new benzamide compound YM-09151 with sulpiride in the treatment of schizophrenia. J Clin Med. 1989;5:2149–75. (in Japanese, Abstract in English).

    Google Scholar 

  • Kudo Y, Nishimura K, Saito M, Otsuki S, Inanaga K, Nakajima T. A double-blind comparative study of Y-516 and haloperidol in the treatment of schizophrenia. J Clin Exp Med. 1990;152:529–43. (in Japanese).

    Google Scholar 

  • Mori A, Kazamatsuri H, Kaneno S, Kamijima K, Kariya T, Murasaki M, Yagi G, et al. A double-blind comparison of a new benzamide compound YM-09151 with haloperidol in the treatment of schizophrenia. Clin Eval. 1989;17:349–77. (in Japanese, Abstract in English).

    Google Scholar 

  • Nakazawa T, Ohara K, Sawa A, Kowatari K, Nomura S, Ijima M, et al. A double-blind comparative study of timiperone and clocapramine in the treatment of schizophrenia. Jpn J Clin Psychiatry. 1982;11:101–15. (in Japanese).

    Google Scholar 

  • Nakazawa T, Oohara K, Nakajima M. Comparative study on clinical effects of timiperone injection and sulpiride injection for schizophrenia. J Clin Med. 1985;1:235–47. (in Japanese, Abstract in English).

    Google Scholar 

  • Okada M, Sarai K, Kodama N, Ishizu H, Sone T, Nakahara T, et al. Comparison of therapeutic effect of zotepine and tiotixene in schizophrenia. J Clin Psychiatry. 1980;22:947–65. (in Japanese).

    Google Scholar 

  • Setoguchi M, Sakamori M, Takehara S, Fukuda T. Effects of iminodibenzyl antipsychotic drugs on cerebral dopamine and α-adrenergic receptors. Eur J Pharmacol. 1985;112:313–22.

    Article  CAS  Google Scholar 

  • Shimomura K, Sato H, Hirai O, Mori J, Tomoi M, Terai T, Katsuki S, Motoyama Y, Ono T. The central anti-serotonin activity of zotepine, a new neurotropic in rats. Jpn J Pharmacol. 1982;92:405–12.

    Article  Google Scholar 

  • Tachizawa H, Sudo K, Sano M. Effect of timiperone on 3H-spiroperidol binding to rat striatal dopamine receptors. Eur J Pharmacol. 1979;59:245–51.

    Article  CAS  Google Scholar 

  • Takahashi R, Inanaga K, Samejima K, Sarai K, Asada S, Ootsuki S, Nkano S. A multi-center comparative double-blind study of a new butyrophenone derivative, timiperone and perphenazine. Jpn J Clin Exp Med. 1982;56:939–51. (in Japanese).

    Google Scholar 

  • Takahashi R, Yoshimoto S, Inanaga K, Ootsuki S, Samejima K, Sarai K, Nakane M, Asada S, Ogawa N. Double-blind comparison study of timipelon injection with haloperidol injection in Schizophrenia. J Clin Psychiatry. 1986;28:559–72. (in Japanese).

    Google Scholar 

  • Terai M, Usuda M, Maeno H, Kuroiwa I, Noshiro O. Selective binding of YM-09151-2, a new potent neuroleptic, to D2-dopaminergic receptors. Jpn J Pharmacol. 1983;33:749–55.

    Article  CAS  Google Scholar 

  • Uchida S, Honda F, Otsuka M, Satoh Y, Mori J, Hitomi M. Pharmacological study of [2-chloro-ll-(2-dimethyl-aminoethoxt)-dibenzo[b,f]thieno](zotepine), new neuroleotic drug. Arzneim-Forsch. 1979;29:1588–94.

    CAS  Google Scholar 

  • Ueda I, Sato Y, Maeno S, Umino S. Synthesis and pharmacological properties of 8-chlor-10-(2-dimethylaminoethoxy)dibenzo[b,f]thiepin and related compounds. Neurotropic and psychotropic agents. III. Chem Pharm Bull. 1978;26:3058–70.

    Article  CAS  Google Scholar 

  • Usuda S, Nishikori K, Noshiro O, Maeno H. Neuroleptic properties of cis N-(1-benzyl-2-methyl-pyrrolidine-3-yl)-5-chloro-2-methoxy-4-methylamino-benzamide(YM-09151-2) with selective antidopaminergic activity. Psychopharmacology. 1981;73:103–8.

    Article  CAS  Google Scholar 

  • Yamasaki T, Kojima H, Sakurai T, Kasahara A, Watanabe S, Fujiwara M, Ueki S. Pharmacological studies on timiperone, a new neurotropic dug. Arzneim-Forsch. 1981;31:701–7.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, Tokyo Women’s University, Tokyo, Japan

    Ken Inada

  2. Institute of CNS Pharmacology, Kanagawa, Japan

    Mitsukuni Murasaki

  3. Institute of CNS Pharmacology, Tokyo, Japan

    Jun Ishigooka

Authors
  1. Ken Inada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mitsukuni Murasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun Ishigooka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ken Inada .

Editor information

Editors and Affiliations

  1. Dept Psychiatry , Psychosomatics & Psychotherapy, University of Würzburg, Medical School Clinical Neurochemistry, Würzburg, Germany

    Peter Riederer

  2. Inst für Psychologische Medizin, Haag, Bayern, Germany

    Gerd Laux

  3. Fujita Health University School Medicine, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

  4. Center Translational Res Neurol Diseases, Dalian Med Uni Shanghai Inst Health Sc Center Translational Res Neurol Diseases, Dalian, China

    Weidong Le

  5. Würzburg, Bayern, Germany

    Christian Riederer

Section Editor information

  1. Department of Psychiatry, University Hospital Leipzig, Leipzig, Germany

    Frank Schmidt

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Inada, K., Murasaki, M., Ishigooka, J. (2021). First-Generation Antipsychotics as a Bridge to Second-Generation Antipsychotics in the Japanese Pharmaceutical Industry: Mosapramine, Timiperone, Zotepine, and Nemonapride. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_417-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-56015-1_417-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-56015-1

  • Online ISBN: 978-3-319-56015-1

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation