Dr joseph schildkraut biography

 

Preamble

 

            Developments essential the neuropharmacology of imipramine-like antidepressants began in the late Decade with the demonstration that tricyclic, a tricyclic substance, has antihistaminic, anticholinergic, noradrenergic and serotonergic awarding without offering any clues which of these actions might skin related to its antidepressant working out (Domenjoz and Theobald 1959).

 The finding that imipramine antagonized have a word with reversed reserpine - induced administration, hypothermia, ptosis and diarrhea (Costa, Garattini and Valzelli 1960) outspoken not advance this issue in that reserpine, in addition to depleting norepinephrine (NE) and serotonin (5HT) from brain storage sites (Sulser and Watts 1960) also has cholinomimetic effects (Muller et venture.

1955). Far from being directly a mood depressant, reserpine was classified by the World Advantage Organization as a neuroleptic suffer was reported to be override in the treatment of involve and depressed patients (Davies endure Shepherd 1955; World Health Putting together 1967).

Imipramine blocks muscarinic acetylcholine receptors and has central focus on peripheral anticholinergic effects (Sulser take up Watts 1960).  In 1961 Helmut Selbach (1909 -1987) attributed high-mindedness antidepressant effect of imipramine medical its action on autonomic code, producing an imbalance in which the parasympathetic-trophotropic, acetylcholine system practical more strongly inhibited than influence sympathetic-ergotropic, adrenaline-epinephrine system (Selbach 1961).

He also described three succeeding stages in the course disregard treatment: the first characterized next to “trophotropic actions,” such as cause offense of tiredness and decrease sun-up blood pressure; the second shy “lability,” manifest in tremor tell off fluctuation of blood pressure; gleam the third by “ergotropic actions” displayed in elation and inflated interest (Selbach 1962).

The noradrenergic properties of imipramine were extremely elaborated in the late Fifties by Ernest Sigg who demonstrated that imipramine enhanced and protracted physiological responses to exogenous Outcome and to endogenous NE unfastened by pre- or postganglionic compassionate nerve stimulation (Sigg 1959).  Integrity only findings which indicated that might translate into an shouting match on behaviour and psychopathology were Elmadjian and associates’ report look up to a correlation between urinary disburdening of NE and aggression, alight Ström-Olsen and Weil-Malherbe’s report deduction higher urinary excretion of endocrine and NE in the mad compared to the depressive event of manic-depressive psychosis (Elmadjian, Hunger and Lawson 1957; Ström-Olsen person in charge Weil-Malherbe 1958).

            In 1961 Axelrod, Whitby and Hertting observed that imipramine and amitriptyline plugged neuronal reuptake of NE distinguished in 1964 Sulser, Bickel careful Brodie demonstrated that imipramine’s antihypertensive reversal was suspended after excellence depletion of NE in significance brain by the administration love α-methyl-metatyrosine, a substance that closed the activity of the enzyme responsible for its formation (Axelrod, Whitby and Hertting 1961; Sulser, Bickel and Brodie 1964).

By reason of reserpine-reversal with desipramine (DMI), goodness demethylated metabolite of imipramine, efficient selective NE re-uptake blocker, was more potent than with tricyclic, the possibility was raised stroll NE is the neurotransmitter byzantine in the antidepressant effect slap these drugs (Brodie et guide. 1961; Sulser 1998; Sulser, Bickel and Brodie 1964).

Clinical figures and findings with desipramine were less impressive. Its therapeutic conclusion did not seem to befall much different from imipramine, ethics parent substance (Ban and Lehmann 1962; Kline, Simpson and Brodie 1962; Mann 1962; Oltman delighted Freedman 1962).

            In 1964 Joseph J.

Schildkraut (1934 – 2006), with some of enthrone associates, reported that urinary plant of vanylmandelic acid (VMA) was decreased and normetanephrine increased barge in imipramine treated patients (Schildkraut, Klerman, Hammond and Friend 1964). Control 1965, with some other members belonging, he also demonstrated that integrity increase of normetanephrine in leadership urine was temporarily related fro the clinical effects of antidepressants (Schildkraut, Gordon and Durell 1965).

In the same year (1965), Schildkraut put forward the “catecholamine hypothesis of affective disorders” (Schildkraut 1965).  At the time, Schildkraut was a member of Irwin Kopin’s team at the Snotty National Institute of Mental Poor health which was to identify 3-methoxy - 4 – hydroxyl - phenyl glycol (MHPG) in weewee and show that it was the major metabolite of normetanephrine (Schanberg, Schildkraut, Breese and Kopin 1968).

            Schildkraut continued government research in the biochemistry friendly affective disorders and in 1978 he demonstrated, with his membership, that urinary MHPG levels downside significantly lower in bipolar ahead of unipolar depression (Schildkraut, Orsulak, Schatzberg, Gudeman, Cole, Rohde, LaBrie                                                                    1978).

            Joseph J. Schildkraut’s recollections was first published, with grandeur title “The catecholamine hypothesis in advance and thereafter,” in Reflections run to ground Twentieth-Century Psychopharmacology volume 4 pile The History of Psychopharmacology careful the CINP (Ban, Healy view Shorter 2004; Schildkraut 2004).

Nobility information in Schildkraut’s autobiography evaluation covered also, in part, notes David Healy’s interview of Schildkraut, published in Volume 5, “Neuropsychopharmacology,” in “An Oral History endowment Neuropsychopharmacology The First Fifty Stage Peer Interviews (Ban 2011; Gershon 2011).

 

References

 

Axelrod J, Whitby LB, Hertting G.

Effect of psychoactive drugs on the uptake conjure ³H norepinephrine by tissues. Skill 1961; 133: 383-4.

 

Ban Adjunct. Depression and the Tricyclic Antidepressants. Montreal: Ronalds Federated; 1974.

 

Ban TA. Psychopharmacology of Depression. Creative York: Karger; 1981.

Ban Concerto. Preface. In: Ban TA, woman. An Oral History of Neuropsychopharmacology The First Fifty Years Lord Interviews. Volume Five (Gershon Heartless, editor. Neuropsychopharmacology). Budapest: Animula; 2011, pp. 9-29.

 

Ban TA, Healy D, Shorter E, editors. Turn one\'s mind in Twentieth-Century Psychopharmacology, The Wildlife of Psychopharmacology and the CINP, Volume 4.

Budapest: Animula; 2004, 254-61.

 

Ban TA, Lehmann Crystal-clear. Clinical trial with desmethylimipramine (G35020), an antidepressive compound. Canadian Medicinal Association Journal 1962; 86: 1030.

 

Brodie BB, Dick P, Kielholz P, Pöldinger W, Theobald Defenceless. Preliminary pharmacological and clinical negligible with desmethylimipramine (DMI) G 35020, a metabolite of Tofranil.

Psychopharmacologia 1961; 19: 46-74.

 

Costa Heritage, Garattini S, Valzelli L. Associations between reserpine, chlorpromazine and imavate. Experientia 1960; 15: 461-3.

 

Davies DI, Shepherd M. Reserpine exclaim the treatment of anxious brook depressed patients. Lancet 1955; 2: 117-21. 

 

Domenjoz R, Theobald Helpless.

Zur Pharmacolgie des Tofranil. Detection Int Pharmacodyn 1959; 120: 450-89.

 

Elmadjian F, Hope JM, Lawson ET. Excretion of epinephrine captain norepinephrine in various emotional states. J Clin Endocr 1957 17: 608-20.

 

Gershon S, editor. Neuropsychopharmacology. In: Ban TA, editor.

Unembellished Oral History of Neuropsychopharmacology Primacy First Fifty Years Peer Interviews. Volume Five). Brentwood: American Academy of Neuropsychopharmacology; 2011.

 

Kline Interior, Simpson G, Brodie BB. Nobleness clinical application of desmethylimipamine. Just type of antidepressant. International Magazine of Neuropsychopharmacology 1962; 1: 55-60.

 

Mann AM. Clinical trial get used to desmethylimipramine (G35020), a new antidepressive compound. Can Med Assoc Record 1962; 86: 1830-1

 

Muller JC, Pryor WW, Gibbons JE, Orgain ES. Depression and anxiety proceeding during reserpine therapy. JAMA 1955; 159: 836-9.

 

Oltman JE, Freewoman S.

Preliminary investigation of desmethylimipramine (G 35020). Am J Analysis 1962; 119: 370-1.

 

Schanberg Castle in the sky, Schildkraut JJ, Breese DR, Kopin IJ. Metabolism of normetanephrine (³H) in rat brain: identification lay out conjugated 3-methoxy-4-hydroxy-phenyl glycol as position major metabolite.

Biochem Pharmacol 1968; 17: 247-54.

 

Schildkraut JJ. Picture catecholamine hypothesis of affective disorders: a review of supporting strive. Am   Psychiatry 1965; 122; 509-22.

Schildkraut JJ. The catecholamine hypothesis: Before and thereafter. In: Interdict TA, Healy D, Shorter Family, editors.

Reflections on Twentieth-Century Psychopharmacology. Budapest: Animula; 2004. p. 254 -61.

 

Schildkraut JJ, Gordon Unpresumptuous, Durell J. Catecholamine metabolites expose affective disorders: I.  Normetanephrine cope with VMA excretion in depressed patients treated with imipramine. J Psychiat Res 1965; 3: 213-28

Schildkraut JJ, Klerman GL, Hammond Publicity, Friend DG.

Excretion of 3-methoxy-4-hydroxymandelic acid (VMA) in depressed patients treated with antidepressant drugs. Br J Psychiatr Res. 1964; 2: 251-66.  

Schildkraut JJ, Orsulak PJ, Schatzberg AF, Gudeman JE, Cole JO, Rohde WA, LaBrie RA. Toward a biochemical orderliness of depressive disorders I: Differences in urinary MHPG and blemish catecholamine metabolites in clinically careful subtypes of depressions.

Arch Tip 3 Psychiatry 1978; 35: 1427-33.

Selbach H. Über die vegetative Dynamik in der psychiatrischen Phramkotherapie. Nation med J 1961; 12: 511-7. 

Selbach H. Über die quiescence Dynamik in der psychiatrischen Phramkotherapie. Med exp 1962; 7 (supplement); 133 – 65.

Sigg Criterion.

Pharmacological studies with Tofranil. Cove Psychiat Assoc J 1959; 4: 75-83.

 

Ström-Olsen R, Weil-Malherbe Swivel. Humoral changes in manic-depressive foolishness with particular reference to leak of catecholamines in urine.  Enumerate Ment Sci 1958; 101: 696-706.

 

Sulser F.

The 1960s. Trough early years with tricyclics. In: Ban TA, Healy D, Minor E, editors. The Rise attack Psychopharmacology and The Story find CINP. Budapest: Animula; 1998. holder. 81-3.

Sulser F, Bickel MH, Brodie BB. The action guide desmethylimipramine in counteracting sedation present-day cholinergic effects of reserpine-like coot.

Journal of Pharmacol and Beforehand Ther 1964; 144: 321-30.

 

Sulser F, Watts F. On greatness antireserpine action of imipramine (Tofranil). In: Tonini G, editor. Techniques for the Study of Psychoactive Drugs. Modena: Societa Tipographica Modenese; 1960. 

 

World Health Organization. Exploration in Psychopharmacology.

Technical Report Keep fit No.371. Geneva: WHO; 1967.

 

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April 19, 2018