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Thomas A. Ban: Development of our Vocabulary

Pharmacopsychology, Behavioral Pharmacology, Neuropharmacology, Psychopharmacology and Neuropsychopharmacology

Thomas A. Ban

The term “psychopharmacology” was introduced in 1920 by David Macht, an American pharmacologist at Johns Hopkins University, for describing the effects of the antipyretics, quinine and acetylsalicylic acid on neuromuscular coordination tests (Macht 1920). The term was used as a synonym for “pharmacopsychology,” a term, introduced in 1892 by Emil Kraepelin, for describing the “psychic effects” of morphine, alcohol, paraldehyde, chloral hydrate, ether and amyl-nitrate. The scope of psychopharmacology was gradually extended to all experimental investigations of the psychometric and “psychic” effects of drugs. By the 1940s, with the availability of lysergic acid diethylamide, psychopharmacology embraced research with psychotomimetics (also referred to as hallucinogens, psychodysleptics, psychotopathics, etc.), and by the 1950s, it included clinical investigations of the therapeutic effects of a rapidly growing number of new psychotherapeutic drugs used in the treatment of psychiatric disorders (Ban 2004). Simultaneously, with the availability of effective psychotropic drugs for treatment of mental illness, such as chlorpromazine, reserpine, imipramine, and iproniazid, there was a shift in the understanding of the nature of synaptic transmission from a purely electrical to a chemically mediated event; by the end of the 1950s, seven neurotransmitters had been identified in the central nervous system: acetylcholine, epinephrine, dopamine, γ-amino butyric acid, norepinephrine, serotonin, i.e., 5-hydroxytryptamine, and substance P (Ban 2006). Recognition of chemical mediation at the site of the synapse, coupled with the introduction of the spectrophotofluorimeter (Bowman, Caulfield and Udenfriend  1955), an instrument with a resolution power to detect drug-induced changes in the concentration of neurotransmitter monoamines and their metabolites, led to the development of neuropharmacology, a branch of pharmacology that deals with the detection and identification of structures responsible for the psychotropic effects of centrally acting drugs. Previously, research dealing with centrally acting drugs was restricted to behavioral pharmacology (Simon 1998) and neurophysiological measures. Spectrophotofluorimetry provided direct access to the detection of the biochemical changes that might be responsible for therapeutic effects. Spectrophotofluorimetry has also opened the path for the development of neuropsychopharmacology, a new discipline that studies the relationship between neuronal and mental processing in the brain with the employment of centrally acting drugs (Ban 2004).

The first neuropharmacological studies with the aid of spectrophotofluorimetry revealed that: (1) administration of reserpine, a Rauwolfia alkaloid, produced a decrease in brain serotonin and norepinephrine levels (Pletscher Shore and Brodie 1955; Holzbauer and Vogt 1956), (2) administration of iproniazid, an inhibitor of the enzyme responsible for the breakdown of monoamines (Zeller et al 1953), increased brain serotonin levels (Pletscher 1956); (3) pre-treatment with iproniazid attenuated reserpine-induced depletion of serotonin and catecholamines (Besendorf and Pletscher 1956; Carlsson et al 1957),  and (4) only those Rauwolfia alkaloids Brodie, Shore and Pletscher 1956) and benzoquinolizines (Pletscher 1957)  (a group of synthetic substances) that depleted serotonin had tranquilizing, or sedating, action. A possible relationship between mood and cerebral monoamine levels was based on clinical reports which indicated that treatment with iproniazid induced euphoria, a feeling of well-being in some tubercular patients (Flaherty 1952; Selikoff and Robitzek 1952), whereas treatment with reserpine induced depressed mood or dysphoria in about 15% of hypertensive patients (Freis 1954; Mueller eta al 1955).  The “birth” of neuropsychopharmacology in the mid-1950s was the result of combining these clinical observations with findings in neuropharmacological research (Ban 2008). The foundation of the new discipline was tenuous. There were reports that isoniazid, the parent substance of iproniazid, had similar effects on mood to those of iproniazid without virtually any effect on monoamine oxidase activity (Delay, Laine and Buisson 1952; Salzer and Lurie 1953, 1955). There was also a report on the favorable effects of reserpine in anxious and depressed patients (Davies and Shepherd 1955; Healy 1997).

One of the first to recognize that neuropsychopharmacology opened up a new perspective in the understanding of psychiatric illness was Abraham Wikler, an American psychiatrist (Hollister 1996). In his monograph on The Relation of Psychiatry to Pharmacology, he suggested that studying the mode of action of psychotropic drugs with known therapeutic effects might provide information on the biochemical basis of mental disorders (Wikler 1957). By generating information on molecular changes in psychiatric illness, findings in neuropsychopharmacological research were to guide the development of rational drug treatments. The notion that drugs with known therapeutic effects might provide the key for bridging the gap between neuronal processing and mental pathology has remained the driving force for research in the new field.

References

Ban TA. Neuropsychopharmacology and the history of phramacotherapy in psychiatry. A review of developments in the 20th century. In: Ban TA, Healy D, Shorter E, editors. Reflections on Twentieth-Century Psychopharmacology. Budapest: Animula; 2004. p. 697–720.

Ban TA. Academic psychiatry and the pharmaceutical industry. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 429–41.

Ban, T.A. The birth of neuropsychopharmacology. Neuropsychopharmacol Hung 2008; 3(Suppl 2): S12–3.

Besendorf H, Pletscher A. Beeinflussung zentraler Wirkungen von Reserpin und 5-Hydroxytryptamin durch Isonikotinsäurehydrazide. Helv Physiol Pharmacol Acta 1956; 14: 383–90.

Bowman RL, Caulfield PA, Udenfriend S. Spectrophotometric assay in the visible and ultraviolet. Science 1955; 122: 32–3.

Brodie BB, Shore PA, Pletscher A. Limitation of serotonin releasing activity to those alkaloids possessing tranquilizing action. Science 1956; 123: 992–3.

Carlsson A, Rosengren E, Bertler A, Nilsson, J. Effects of reserpine on the metabolism  of catecholamines. In: Garattini S, Ghetti V, editors. Psychotropic Drugs. Amsterdam: Elsevier; 1957. p. 363–72.

Davies DL, Shepherd M. Reserpine in the treatment of anxious and depressed patients. Lancet 1955; 2: 117–20.

Delay J, Laine B, Buisson JF. Note concernant l’action de l’isonicotinyl dans le traitement des états dépressives. Ann Med Psychol (Paris) 1952; 110; 689–92.

Flaherty JA. The psychiatric use of isonicotinic acid hydrazide: a case report. Del Med J 1952; 24: 298–300.

Freis ED. Mental depression in hypertensive patients treated for long periods with large doses of reserpine. N Engl J Med 1954; 251: 1006–8.

Healy D. The Antidepressant Era. Cambridge: Harvard University Press; 1997. p. 72–4.

Hollister LE. Review of Wikler’s The Relation of Psychiatry to Pharmacology. In: Ban TA, Ray OS, editors. A History of the CINP. Nashville: JM Productions; 1996. p. 339–43.

Holzbauer M, Vogt M. Depression by reserpine of the noradrenaline concentration in the hypothalamus of the rat. J Neurochem 1956; 1: 8–11.

Kraepelin E. Über die Beeinflussung einfacher psychischer Vorgänge durch einige Arzneimittel. Jena: Fischer; 1892.

Macht DL. Contributions to psychopharmacology. Bull JohnsHopkins Hosp 1920; 31: 167-73.

Mueller JC, Pryor WW, Gibbons JJ, Orgain ES. Depression and anxiety occurring during Rauwolfia therapy. JAMA 1955; 159: 836–9.

Pletscher A. Beeinflussung des 5-Hydroxytryptamin-stoffwechsels im Gehirn durch Isonikotinsäurehydrazide. Experientia 1956; 12: 479–80.

Pletscher A. Release of 5-hydroxytryptamine by benzoquinolizine derivatives with sedative action. Science 1957; 126: 507–8.

Pletscher A, Shore PA, Brodie BB. Serotonin release as a possible mechanism of serotonin action. Science 1955; 122: 374–5.

Salzer HM, Lurie ML. Anxiety and depressive states treated with isonicotinyl hydrazide (isoniazid). Arch Neurol Psychiatry 1953; 70: 317–24.

Salzer HM, Lurie ML. Depressive states treated with isonicotinyl hydrazide (isoniazid). Ohio State Med J 1955;51:437–41.

Selikoff IJ, Robitzek FH, Orenstein GG. Treatment of pulmonary tuberculosis with hydrazine derivatives of isonicotinic acid. JAMA 1957; 150: 973–80.

Simon P. Behavioural pharmacology. In: Ban TA, Healy D, Shorter E, editors. The Rise of Psychopharmacology and the Story of CINP. Budapest: Animula; 1998. p. 131–4.

Wikler A. The Relation of Psychiatry to Pharmacology. Baltimore: Williams and Wilkins; 1957.

Zeller EA, Barsky JR, Fouts W, Kirchheimer WP, Van Orden LS. Influence of isonicotinic acid hydrazide (INH) and 1-isonicotinyl-2-isopropyl hydrazide (IIH) on bacterial and mammalian enzymes. Experientia 1952; 8: 349–50.

 

Thomas A. Ban
January 21, 2016