Elsevier

Comprehensive Psychiatry

Volume 40, Issue 6, November–December 1999, Pages 407-414
Comprehensive Psychiatry

A history of antipsychotic drug development

https://doi.org/10.1016/S0010-440X(99)90082-2Get rights and content

Abstract

The history of antipsychotic drug development has had a long and torturous course, often based on chance findings that bear little relationship to the intellectual background driving observations. In 1891, Paul Ehrlich observed the antimalarial effects of methylene blue, a phenothiazine derivative. Later, the phenothiazines were developed for their antihistaminergic properties. In 1951, Laborit and Huguenard administered the aliphatic phenothiazine, chlorpromazine, to patients for its potential anesthetic effects during surgery. Shortly thereafter, Hamon et al. and Delay et al. extended the use of this treatment in psychiatric patients and serendipitously uncovered its antipsychotic activity. Between 1954 and 1975, about 15 antipsychotic drugs were introduced in the United States and about 40 throughout the world. Thereafter, there was a hiatus in the development of antipsychotics until the introduction of clozapine treatment in the United States in 1990 opened the era of “atypical” antipsychotic drugs, which show a reduced potential to induce extrapyramidal symptoms (EPS), an increased efficacy for the negative symptoms of schizophrenia, no elevation of prolactin after chronic use (except risperidone), and, at least for clozapine, effectiveness in some patients previously regarded as treatment-refractory. This review describes the available atypical antipsychotic drugs and their characteristics, and concludes by highlighting those in the pharmaceutical “pipeline.”

References (63)

  • J.P Swazey

    Chlorpromazine in Psychiatry: A Study in Therapeutic Innovation

    (1974)
  • W.W Shen et al.

    The discoverers of the therapeutic effect of chlorpromazine in psychiatry: qui elaient les vrais premiers praticiens?

    Can J Psychiatry

    (1998)
  • H.E Lehmann et al.

    Authors respond

    Can J Psychiatry

    (1998)
  • W.W Shen

    Pharmacotherapy of schizophrenia: the American current status

    Keio J Med

    (1994)
  • J.E Stähelin et al.

    Largactil: ein neues vegetatives dampfunsmittel bei psychischen stornugen

    Schweiz Med Wochenschr

    (1953)
  • H.E Lehmann et al.

    Chlorpromazine: new inhibiting agent for psychomotor excitement and manic states

    Arch Neurol Psychiatry

    (1954)
  • H Lehmann

    Psychopharmacology

  • N.W Winkelman

    Chlorpromazine in the treatment of neuropsychiatric disorders

    JAMA

    (1954)
  • J Elkes et al.

    Effects of chlorpromazine on the behavior of chronically over active psychotic patients

    BMJ

    (1954)
  • J.F Casey et al.

    Drug therapy in schizophrenia: a controlled study of the relative effectiveness of chlorpromazine, promazine, phenobarbital and placebo

    Arch Gen Psychiatry

    (1960)
  • J.F Casey et al.

    Treatment of schizophrenic reactions with phenothiazine derivatives: a comparative study of chlorpromazine, triflupromazine, mepazine, prochlorperazine, perphenazine, and phenobarbital

    Am J Psychiatry

    (1960)
  • C.L Zirkle et al.

    Antipsychotic drugs

  • W.W Shen

    The need for depot atypical antipsychotics in the US

    Psychiatr Serv

    (1998)
  • H Steck

    Le syndrome extrapyramidal et diencephalique au Largactil et au Serpasil

    Ann Med Psychol (Paris)

    (1954)
  • F.J Ayd

    A survey of drug-induced extrapyramidal reactions

    JAMA

    (1961)
  • H.J Haase et al.

    The Action of Neuroleptic Drugs: A Psychiatric, Neurologic, and Pharmacological Investigation

    (1958)
  • H Hippius

    The founding of the CINP and the discovery of clozapine

  • H Hippius

    The history of clozapine

    Psychopharmacology

    (1989)
  • J Sigwald et al.

    Quartre cas de dyskinésie, facio-bucco-linguo-masticatrice ä l'évolution prolongée secondaire ä un treatment par les neuroleptiques

    Rev Neurol (Paris)

    (1959)
  • H Gross et al.

    Das Wirkungprofil eines chemischen neuartigen Breitband-neuroleptikums der Dibenzodiazepingruppe

    Wien Med Wochenschr

    (1966)
  • Cited by (206)

    • Treatment of cancer with antipsychotic medications: Pushing the boundaries of schizophrenia and cancer

      2022, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      The first began with the synthesis of organic dyes, particularly the fabric dye, methylene blue (MB). Several excellent reviews cover the developments of MB (Howland, 2016a; b; Schirmer et al., 2011), phenothiazines (Frankenburg and Baldessarini, 2008; López-Muñoz et al., 2005; Ohlow and Moosmann, 2011) and antipsychotics starting with the first phenothiazine antipsychotic, chlorpromazine (Frankenburg and Baldessarini, 2008; López-Muñoz et al., 2005; Shen, 1999). Schirmer et al. (Schirmer et al., 2011) describe MB as the first synthetic drug in medical history beginning with its use in treating malaria in 1891 after MB’s synthesis in 1876 by Heinrich Caro (1834–1910) (Frankenburg and Baldessarini, 2008).

    View all citing articles on Scopus
    View full text