Skip to main content
SpringerLink
Log in

Pharmacogenetic aspects of psychoactive drugs: Facts and fancy

  • Reviews
  • Published:
Humangenetik Aims and scope Submit manuscript

Summary

Psychopharmacogenetics is an interdisciplinary field involving clinical pharmacology, psychology, psychiatry and human genetics. Our present-day knowledge of genetically determined interindividual variability at the biochemical level makes differences in the metabolism and the pharmacological effects of drugs appear probable. In theory, pharmacogenetic differences are possible in each of the pharmacokinetic parameters (absorption, distribution, metabolism, interaction with the receptor, excretion).

Two fundamental approaches in psychopharmacogenetics have to be differentiated: 1. Influence of genetic factors on the kinetics of a centrally acting drug. 2. Role of genetic factors in the reaction of the central nervous system to psychotropic drugs. Accordingly, findings and observations of genetic interest are summarized.

  1. 1.

    Differences on the basis of metabolism. a) Tricyclic antidepressants. From the genetic point of view the tricyclic antidepressants are the best known psychotropic drugs up to now. The wide interindividual differences in steady-state plasma levels are mainly of genetic origin. b) Polymorphic N-acetyltransferase. This enzyme probably acetylates the MAO inhibitor phenelzine. It is controversial whether serotonin is a physiologic substrate of the polymorphic enzyme. c) Alcohol. Twin studies have revealed the significance of genetic factors in the metabolism of ethanol. d) Diphenylhydantoin. The metabolism of DPH is subject to wide interindividual variation; familial occurrence of slow metabolism has been described. e) Phenothiazines. Various observations and findings make it appear probable that genetic factors are involved in the response to phenothiazines.

  2. 2.

    Differences in the susceptibility to centrally acting drugs with a possible genetic basis. a) Alcohol. Several findings suggest the involvement of genetic factors in the response to alcohol. Genetic factors may also play a role in alcoholism. b) Caffeine. Intrinsic differences in the sensitivity of sites of action in the brain might have a genetic basis. c) Dopamine-β-hydroxylase. The activity of dopamine-β-hydroxylase in human serum which is involved in the synthesis of noradrenaline is under genetic control. It is possible that not only sympathetic nerve activity but also reaction to drugs interfering with this system is genetically controlled. d) Huntington's chorea. A pharmacogenetic approach appears to be most promising for the early diagnosis of Huntington's chorea. e) Drug reactions and personality traits. There are indications of differential effects of psychotropic drugs in different personality types, which might at least in part be under genetic control. f) Drug reactions and EEG. Another promising approach to detection of genetic differences in the response to psychoactive drugs could be the examination of reactions of persons with EEG variants.

Although we do not know very much about the significance of heredity in the response to centrally acting drugs, this field of investigation appears to be promising for the disciplines involved.

Zusammenfassung

Die Pharmakogenetik zentral wirkender Substanzen (Psychopharmakogenetik) ist ein Forschungsgebiet, das zwischen den Disziplinen der klinischen Pharmakologie, Psychologie, Psychiatrie und Humangenetik steht. Unser heutiges Wissen über die genetisch determinierte inter-individuelle Variabilität auf biochemischer Ebene macht Unterschiede im Metabolismus und im pharmakologischen Effekt von Pharmaka wahrscheinlich. Im Prinzip sind pharmakogenetische Unterschiede bei jedem der pharmakokinetischen Faktoren möglich: Resorption, Verteilung, Metabolismus, Bindung an den Receptor, Ausscheidung.

Grundsätzlich sind zwei Ansätze im Rahmen der Psychopharmakogenetik zu unterscheiden: 1. Einfluß genetischer Faktoren auf die Kinetik einer zentral wirkenden Substanz. 2. Einfluß genetischer Faktoren an der Reaktion des ZNS auf zentral wirkende Substanzen. Entsprechend werden Befunde und Beobachtungen aus der Literatur zusammengestellt, die von genetischem Interesse sind.

  1. 1.

    Unterschiede auf metabolischer Basis. a) Tricyclische Antidepressiva. Aus genetischer Sicht sind diese Pharmaka die bisher am besten analysierten, zentral wirkenden Substanzen. Die großen inter-individuellen Unterschiede der Plasmaspiegel unter steady-state-Bedingungen sind hauptsächlich genetischer Natur. b) Die polymorphe N-Acetyltransferase. Dies Enzym acetyliert sehr wahrscheinlich den MAO-Hemmer Phenelzin. Es ist bisher offen, ob Serotonin ein physiologisches Substrat des polymorphen Acetylierungs-Enzyms ist. c) Alkohol. Zwillings-Studien weisen auf die Bedeutung genetischer Faktoren beim Metabolismus von Äthanol hin. d) Diphenylhydantoin. Der Metabolismus von DPH unterliegt einer großen inter-individuellen Variabilität; familiäres Auftreten eines langsamen Abbaus von DPH ist beschrieben worden. e) Phenothiazine. Verschiedene Beobachtungen und Befunde weisen auf die Existenz genetischer Faktoren an der Reaktion auf Phenothiazine hin.

  2. 2.

    Unterschiedliches Ansprechen auf zentral wirkende Substanzen mit eventueller genetischer Bedeutung. a) Alkohol. Eine Reihe von Befunden macht die Beteiligung genetischer Faktoren an der Reaktion auf Alkohol wahrscheinlich. Genetische Faktoren spielen vielleicht auch bei der Entstehung des Alkoholismus eine Rolle. b) Coffein. Die bekannten Unterschiede im Ansprechen auf Coffein können eine genetische Grundlage haben. c) Dopamin-β-hydroxylase. Die Aktivität der Dopamin-β-hydroxylase im Serum des Menschen, die an der Synthese des Noradrenalins beteiligt ist, unterliegt einer genetischen Kontrolle. Vielleicht steht damit nicht nur die Aktivität des sympathischen Nervensystems, sondern auch die Reaktion auf Pharmaka, die auf dieses System einwirken, unter genetischer Kontrolle. d) Huntingtonsche Chorea. Ein pharmakogenetischer Ansatz erscheint für die Frühdiagnose dieser Krankheit am erfolgversprechendsten. e) Psychopharmaka und Persönlichkeit. Es gibt Hinweise für differentielle Effekte psychotroper Substanzen bei verschiedenen Persönlichkeitstypen, die zumindest teilweise genetisch determiniert sein könnten. f) Psychopharmaka und EEG. Ein weiterer vielversprechender Ansatz zum Auffinden genetischer Unterschiede in der Reaktion auf zentral wirkende Substanzen könnte die Untersuchung von Personen mit EEG-Varianten sein.

Trotz unseres heute noch sehr lückenhaften Wissens über die Bedeutung der Genetik für die Reaktion auf zentral wirkende Substanzen ist dieses Forschungsgebiet für alle daran beteiligten Disziplinen vielversprechend für die Zukunft.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahrens, R.: On the forensic-psychiatric significance of alcohol loading tests under EEG control. Electroenceph. clin. Neurophysiol. 30, 269–270 (1971)

    Google Scholar 

  • Alexanderson, B.: Pharmacokinetics of desmethylimipramine and nortriptyline in man after single and multiple oral doses. — A cross-over study. Europ. J. clin. Pharmacol. 5, 1–10 (1972)

    Google Scholar 

  • Alexanderson, B., Borgå, O.: Urinary excretion of nortriptyline and five of its metabolites in man after single and multiple oral doses. Europ. J. clin. Pharmacol. 5, 174–180 (1973)

    Google Scholar 

  • Alexanderson, B., Price Evans, D. A., Sjöqvist, F.: Steady-state plasma levels of nortriptyline in twins: Influence of genetic factors and drug therapy. Brit. med. J. 4, 764–768 (1969)

    Google Scholar 

  • Alexanderson, B., Sjöqvist, F.: Individual differences in the pharmacokinetics of monomethylated tricyclic antidepressants: Role of genetic and environmental factors and clinical importance. Ann. N.Y. Acad. Sci. 179, 739–751 (1971)

    Google Scholar 

  • Angst, J.: A clinical analysis of the effects of tofranil in depression. Longitudinal and follow-up studies. Treatment of blood-relations. Psychopharmacologia (Berl.) 2, 381–407 (1961)

    Google Scholar 

  • Angst, J.: Antidepressiver Effekt und genetische Faktoren. Arzneimittel-Forsch. 14, 496–500 (1964)

    Google Scholar 

  • Åsberg, M., Cronholm, B., Sjöqvist, F., Tuck, D.: The correlation of subjective side-effects with plasma concentrations of nortriptyline. Brit. med. J. 4, 18–21 (1970)

    Google Scholar 

  • Åsberg, M., Price Evans, D. A., Sjöqvist, F.: Genetic control of nortriptyline plasma levels in man: A study of the relatives of propositi with high plasma concentration. J. med. Genet. 8, 129–135 (1971)

    Google Scholar 

  • Ayd, F. J.: A survey of drug-induced extrapyramidal reactions. J. Amer. med. Ass. 175, 1054–1060 (1961)

    Google Scholar 

  • Bönicke, R., Lisboa, B. P.: Über die Erbbedingtheit der intraindividuellen Konstanz der Isoniazidausscheidung. Naturwissenschaften 44, 314 (1957)

    Google Scholar 

  • Bracken, v. H.: Humangenetische Psychologie. In: Humangenetik, ein kurzes Handbuch in fünf Bänden, Becker, P. E., Ed., Vol. I/2. Stuttgart: Thieme 1969

    Google Scholar 

  • Braithwaite, R. A., Goulding, R., Theano, G., Bailey, J., Coppen, A.: Plasma concentration of amitriptyline and clinical response. Lancet 1972I, 1297–1300

  • Brodie, B. B., Cosmides, G. J., Rall, D. P.: Toxicology and the biomedical sciences. Science 148, 1547–1554 (1965)

    Google Scholar 

  • Brodie, B. B., Reid, W. D.: Some pharmacological consequences of species variation in rates of metabolism. Fed. Proc. 26, 1062–1070 (1967)

    Google Scholar 

  • Cederbaum, S.: Tests for Huntington's chorea. New Engl. J. Med. 284, 1045 (1971)

    Google Scholar 

  • Cruz-Coke, R.: Genetic aspects of alcoholism. In: Biological basis of alcoholism, Israel, J., Mardones, J., Eds., pp. 335–363. New York-London-Sidney-Toronto: John Wiley and Sons 1971

    Google Scholar 

  • Cruz-Coke, R., Vareia, A.: Inheritance of alcoholism. Lancet 1966I, 1282–1284

  • Curry, S. H.: The determination and possible significance of plasma levels of chlorpromazine in psychiatric patients. Agressologie 9, 115–121 (1968)

    Google Scholar 

  • Curry, S. H.: Chlorpromazine: Concentration in plasma, excretion in urine and duration of effect. Proc. roy. Soc. Med. 64, 285–290 (1971)

    Google Scholar 

  • Curry, S. H., Davis, J. M., Janowsky, D. S., Marshall, J. H. L.: Factors affecting chlorpromazine plasma levels in psychiatric patients. Arch. gen. Psychiat. 22, 209–215 (1970)

    Google Scholar 

  • Curry, S. H., Marshall, J. H. L.: Plasma levels of chlorpromazine and some of its relatively non-polar metabolites in psychiatric patients. Life Sci. 7, 9–17 (1968)

    Google Scholar 

  • Dancis, J.: Altered drug response in familial dysautonomia. Ann. N.Y. Acad. Sci. 151, 876–879 (1968)

    Google Scholar 

  • Dost, F. H.: Grundlagen der Pharmakokinetik. Stuttgart: Thieme 1968

    Google Scholar 

  • Edwards, J. A., Price Evans, D. A.: Ethanol metabolism in subjects possessing typical and atypical liver alcohol dehydrogenase. Clin. Pharmacol. Ther. 8, 824–829 (1967)

    Google Scholar 

  • Essig, C. F., Fraser, H. F.: Electroencephalographic changes in man during use and with-drawal of barbiturates in moderate dosage. Electroenceph. clin. Neurophysiol. 10, 649–656 (1958)

    Google Scholar 

  • Fenna, D., Mix, L., Schaefer, O., Gilbert, J. A. L.: Ethanol metabolism in various racial groups. Canad. med. Ass. J. 105, 472–475 (1971)

    Google Scholar 

  • Forrest, I. S., Green, D. E.: Phenothiazines: Metabolism and analytical detection. J. forens. Sci. 17, 592–617 (1972)

    Google Scholar 

  • Fuller, J. L., Collins, R. L.: Ethanol consumption and preference in mice: A genetic analysis. Ann. N.Y. Acad. Sci. 197, 42–48 (1972)

    Google Scholar 

  • Gibaldi, M.: Pharmacokinetic aspects of drug metabolism. Ann. N.Y. Acad. Sci. 179, 19–31 (1971)

    Google Scholar 

  • Gillette, J. R.: Factors affecting drug metabolism. Ann. N.Y. Acad. Sci. 179, 43–66 (1971)

    Google Scholar 

  • Goldstein, A.: Wakefulness caused by caffeine. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 248, 269–278 (1964)

    Google Scholar 

  • Goldstein, A., Warren, R., Kaizer, S.: Psychotropic effects of caffeine in man. I. Individual differences in sensitivity to caffeine-induced wakefulness. J. Pharmacol. exp. Ther. 149, 156–159 (1965)

    Google Scholar 

  • Goodman, L. S., Gilman, A.: The pharmacological basis of therapeutics. New York-London-Toronto: MacMillan 1970

    Google Scholar 

  • Goodwin, D. W., Schulsinger, F., Hermansen, L., Guze, S. B., Winokur, G.: Alcohol problems in adoptees raised apart from alcoholic biological parents. Arch. gen. Psychiat. 28, 238–243 (1973)

    Google Scholar 

  • Green, D. E., Forrest, I. S., Forrest, F. M., Serra, M. T.: Inter-patient variation in chlorpromazine metabolism. Exp. Med. Surg. 23, 278–287 (1965)

    Google Scholar 

  • Haase, H.-J., Kapplinghaus, R., Ball, P., Keitel, P., Koch, C. D., Mattke, D., Nöcker, G., Ritter, R., Schönbeck, M., Zahn, M., Zschucke, C. F.: Disposition zur neuroleptischen Schwelle. Pharmakopsychiatrie 1, 45–54 (1968)

    Google Scholar 

  • Harris, H. Hopkinson, D. A.: Average heterozygosity per locus in man: an estimate based on the incidence of enzyme polymorphisms. Ann. hum. Genet. 36, 9–20 (1972)

    Google Scholar 

  • Hollister, L. E., Levy, G.: Kinetics of meprobamate elimination in humans. Chemotherapia (Basel) 9, 20–24 (1964)

    Google Scholar 

  • Israel, Y., Mardones, J.: Biological basis of alcoholism. New York-London-Sidney-Toronto: John Wiley and Sons 1971

    Google Scholar 

  • Ideström, C.-M., Cadenius, B.: Time relations of the effects of alcohol compared to placebo. Psychopharmacologia (Berl.) 13, 189–200 (1968)

    Google Scholar 

  • Ideström, C.-M., Schalling, D.: Objective effects of dexamphetamine and amobarbital and their relations to psychastenic personality traits. Psychopharmacologia (Berl.) 17, 399–413 (1970)

    Google Scholar 

  • Ideström, C.-M., Schalling, D., Carlqvist, V., Sjöqvist, F.: Acute effects of diphenylhydantoin in relation to plasma levels. Psychol. Med. 2, 111–120 (1972)

    Google Scholar 

  • Janke, W.: Experimentelle Untersuchungen zur Abhängigkeit der Wirkung psychotroper Substanzen von Persönlichkeitsmerkmalen. Frankfurt/M.: Akademische Verlagsgesellschaft 1964

    Google Scholar 

  • Johnstone, E., Marsh, W.: Acetylator status and response to phenelzine in depressed patients. Lancet 1973 I, 567–570

    Google Scholar 

  • Kaij, H. L.: Definitions of alcoholism and genetic research. Ann. N.Y. Acad Sci. 197, 110–113 (1972)

    Google Scholar 

  • Kakihana, R., Brown, D. R., McClearn, G. E., Tabeshaw, J. R.: Brain sensitivity to alcohol in inbread mouse strains. Science 154, 1574–1575 (1966)

    Google Scholar 

  • Kalow, W.: Pharmacogenetics. Heredity and the response to drugs. Philadelphia-London: Saunders 1962

    Google Scholar 

  • Kalow, W.: Morphine adaptation, hexobarbital, alcoholism. General remarks. Humangenetik 9, 260–261 (1970)

    Google Scholar 

  • Kaul, P. N., Conway, M. W., Ticku, M. K., Clark, M. L.: Chlorpromazine metabolism. II. Determinatio of nonconjugated metabolites in blood of schizophrenic patients. J. Pharm. Sci. 61, 581–585 (1972a)

    Google Scholar 

  • Kaul, P. N., Ticku, M. K., Clark, M. L.: Chlorpromazine metabolism. V. Disposition of free and conjugated metabolites in blood fractions of schizophrenic patients. J. Pharm. Sci. 61, 1753–1757 (1972b)

    Google Scholar 

  • Klapper, J. A., McColloch, M. A.: Personality and reactivity to stimulants and depressants. J. nerv. ment. Dis. 154, 439–444 (1972)

    Google Scholar 

  • Klawans, H. C., Paulsen, G. W., Barbeau, A.: Predictive test for Huntington's chorea. Lancet 1970 II, 1185–1186

    Google Scholar 

  • Kragh-Sørensen, P., Åsberg, M., Eggert-Hansen, G.: Plasma-nortriptyline levels in endogenous depression. Lancet 1973 I, 113–115

    Google Scholar 

  • Krooth, R.: Molecular models for pharmacological tolerance and addiction. Ann. N.Y. Acad. Sci. 179, 548–560 (1971)

    Google Scholar 

  • Kuhlo, W., Heintel, H., Vogel, F.: The 4–5 c/sec rhytm. Electroenceph. clin. Neurophysiol. 26, 613–618 (1969)

    Google Scholar 

  • Kulenkampff, C., Tarnow, G.: Ein eigentümliches Syndrom im oralen Bereich bei Megaphenapplikation. Nervenarzt 27, 178–180 (1956)

    Google Scholar 

  • Kutt, H., Biochemical and genetic factors regulating dilantin metabolism in man. Ann. N.Y. Acad. Sci. 179, 704–722 (1971)

    Google Scholar 

  • Kutt, H., Wolk, M., Scherman, R., McDowell, F.: Insufficient parahydroxylation as a cause of diphenylhydantoin toxicity. Neurology (Minneap.) 14, 542–548 (1964)

    Google Scholar 

  • Levy, G., Gibaldi, M.: Pharmacokinetics of drug action. Ann. Rev. Pharmacol. 12, 85–98 (1972)

    Google Scholar 

  • March, J. E., Donato, D., Turano, P., Turner, W. J.: Interpatient variation and significance of plasma levels of chlorpromazine in psychotic patients. J. Med. 3, 146–162 (1972)

    Google Scholar 

  • McClearn, G. E.: Genetics as a tool in alcohol research. Ann. N.Y. Acad. Sci. 197, 26–31 (1972)

    Google Scholar 

  • Meier, H.: Experimental pharmacogenetics. Physiopathology of heredity and pharmacologic responses. New York-London: Academic Press 1963

    Google Scholar 

  • Meyer, R. E., DiMascio, A., Stifler, L.: Personality differences in the response to stimulant drugs administered during a sleep-deprived state. J. nerv. ment. Dis. 150, 91–99 (1970)

    Google Scholar 

  • Motulsky, A. G.: Drug reactions, enzymes and biochemical genetics. J. Amer. med. Ass. 165, 835–837 (1957)

    Google Scholar 

  • Motulsky, A. G.: History and current status of pharmacogenetics. Proc. Fourth Int. Congr. Human Genet., Paris 6.–11. Sept. 1971, Excerpta Medica 1972

  • Müller-Küppers, M., Vogel, F.: Über die Persönlichkeitsstruktur von Trägern einer seltenen erblichen EEG-Variante. Jb. Psychol. Psychother. Med. Anthropol. 12, 75–100 (1965)

    Google Scholar 

  • Munkelt, P., Lienert, G. A., Frahm, M., Soehring, K.: Geschlechtsspezifische Wirkungsunterschiede der Kombination von Alkohol und Meprobamat auf psychisch stabile und labile Versuchspersonen. Arzneimittel-Forsch. 12, 1059–1065 (1962)

    Google Scholar 

  • Munkelt, P., Lienert, G. A.: Blutalkoholspiegel und psychophysische Konstitution. Arzneimittel-Forsch. 14, 573–575 (1964)

    Google Scholar 

  • Myrianthopoulos, N. C., Kurland, A. A., Kurland, L. T.: Hereditary predisposition in drug-induced parkinsonism. Arch. Neurol. 6, 5–9 (1962)

    Google Scholar 

  • Nies, A., Robinson, D. S., Lamborn, K. R., Lampert, R. P.: Genetic control of platelet and plasma monoamine oxidase activity. Arch. gen. Psychiat. 28, 834–838 (1973)

    Google Scholar 

  • Omenn, G. S.: Genetic approaches to the syndrome of minimal brain dysfunction. Ann. N.Y. Acad. Sci. 205, 212–222 (1973)

    Google Scholar 

  • Omenn, G. S., Motulsky, A. G.: A biochemical and genetic approach to alcoholism. Ann. N.Y. Acad. Sci. 197, 16–23 (1972)

    Google Scholar 

  • Pare, C. M. B., Mack, J. W.: Differentiation of two genetically specific types of depression by the response to antidepressant drugs. J. med. Genet. 8, 306–309 (1971)

    Google Scholar 

  • Pare, C. M. B., Rees, L., Sainsbury, M. J.: Differentiation of two genetically specific types of depression by the response to anti-depressants. Lancet 1962 II, 1340–1343

  • Penrose, L. S.: Measurement of pleiotropic effects in phenylketonuria. Ann. Eugen. (Lond.) 16, 134–141 (1951/52)

    Google Scholar 

  • Perry, T. L., Hansen, S., Kloster, M.: Huntington's chorea: Deficiency of aminobutyric acid in brain. New Engl. J. Med. 288, 337–342 (1973)

    Google Scholar 

  • Pharmacogenetics. WHO techn. Rep. Ser., No. 524 (1973)

  • Planz, G., Palm, D.: Acute enhancement of dopamine-β-hydroxylase activity in human plasma after maximum work load. Europ. J. clin. Pharmacol. 5, 255–258 (1973)

    Google Scholar 

  • Price Evans, D. A., Davidson, K., Pratt, R. T. C.: The influence of acetylator phenotype on the effect of treating depression with phenelzine. Clin. Pharmacol. Ther. 6, 430–435 (1965)

    Google Scholar 

  • Price Evans, D. A., Manley, K., McKusick, V. A.: Genetic control of isoniazid metabolism in man. Brit. med. J. 2, 485–491 (1960)

    Google Scholar 

  • Remmer, H., Hirschmann, J., Greiner, I.: Die Bedeutung von Kumulation und Elimination für die Dosierung von Phenytoin (Diphenylhydantoin). Dtsch. med. Wschr. 94, 1265–1272 (1969)

    Google Scholar 

  • Ross, S. B., Wetterberg, L., Myrhed, M.: Genetic control of plasma dopamine-β-hydroxylase. Life Sci. 12, 529–532 (1973)

    Google Scholar 

  • Safer, D. J.: A familial factor in minimal brain dysfunction. Behav. Genet. 3, 175–186 (1973)

    Google Scholar 

  • Scholoot, W.: Pharmakogenetische und biochemische Untersuchungen einer N-Acetyltransferase. Habilitationsschrift, Hamburg 1970

  • Schloot, W., Tigges, F.-J., Blaesner, H., Goedde, H. W.: N-acetyltransferase and serotonin metabolism in man and other species. Hoppe-Seylers Z. physiol. Chem. 350, 1353–1361 (1969)

    Google Scholar 

  • Schuckit, M. A.: Family history and half-sibling research in alcoholism. Ann. N.Y. Acad. Sci. 197, 121–125 (1972)

    Google Scholar 

  • Sidell, F. R., Pless, J. E.: Ethyl alcohol: Blood levels and performance decrements after oral administration to man. Psychopharmacologia (Berl.) 19, 246–261 (1971)

    Google Scholar 

  • Sjöqvist, F.: A pharmacokinetic approach to the treatment of depression. Int. Pharmacopsychiat. 6, 147–169 (1971)

    Google Scholar 

  • Sjöqvist, F., Alexanderson, B., Åsberg, M., Bertilsson, L., Borgå O., Hamberger, B., Tuck, D.: Pharmacokinetics and biological effects of nortriptyline in man. Acta pharmacol. (Kbh.) 29, Suppl. 3, 255–280 (1971)

    Google Scholar 

  • Sjöqvist, F., Hammar, W., Ideström, C.-M., Lind, M., Tuck, D., Åsberg, M.: Plasma level of mono-methylated tricyclic antidepressants and side-effects. In: Excerpta Medical Internat. Congr. Ser. 145, 246–257 (1968)

  • Uhr, L., Miller, J. G. (Eds.): Drugs and behaviour. New York-London-Sidney: John Wiley and Sons 1960

    Google Scholar 

  • Vesell, E. S.: Introduction: genetic and environmental factors affecting drug response in man. Fed. Proc. 31, 1253–1269 (1972)

    Google Scholar 

  • Vesell, E. S.: Advances in pharmacogenetics. Progr. med. Genet. 9, 291–367 (1973)

    Google Scholar 

  • Vesell, E. S., Page, J. G.: Genetic control of the phenobarbital-induced shortening of plasma antipyrine half-lives in man. J. clin. Invest. 48, 2202–2209 (1969)

    Google Scholar 

  • Vesell, E. S., Page, J. G., Passananti, T. G.: Genetic and environmental factors affecting ethanol in man. Clin. Pharmacol. Ther. 12, 192–201 (1971)

    Google Scholar 

  • Vogel, F.: Moderne Probleme der Humangenetik. Ergebn. inn. Med. Kinderheilk. 12, 52–125 (1959)

    Google Scholar 

  • Vogel, F.: The genetic basis of the normal human electroencephalogram (EEG). Humangenetik 10, 91–114 (1970)

    Google Scholar 

  • Walter, C. J. S.: Clinical significance of plasma imipramine levels. Proc. roy. Soc. Med. 64, 282–285 (1971)

    Google Scholar 

  • Weinshilboum, R. M., Axelrod, J.: Reduced plasma dopamine-β-hydroxylase activity in familial dysautonomia. New Engl. J. Med. 285–942 (1971)

  • White, T. A., Jenne, J. W., Price Evans, D. A.: Acetylation of serotonin in vitro by a human N-acetyltransferase. Biochem. J. 113, 721–725 (1969)

    Google Scholar 

  • Williams, R. T., Parke, D. V.: The metabolic fate of drugs. Ann. Rev. Pharmacol. 4, 85–114 (1964)

    Google Scholar 

  • Winokur, G.: X-borne recessive genes in alcoholism. Lancet 1967 II, 466

    Google Scholar 

  • Winokur, G., Rimmer, J., Reich, T.: Alcoholism IV. Is there more than one type of alcoholism? Brit. J. Psychiat. 118, 525–531 (1971)

    Google Scholar 

  • Wolf, P. H.: Ethnic differences in alcohol sensitivity. Science 175, 449–450 (1972)

    Google Scholar 

  • Wolff, P. H.: Vasomotor sensitivity to alcohol in diverse mongoloid populations. Amer. J. hum. Genet. 25, 193–199 (1973)

    Google Scholar 

  • Wooley, D. W.: The biochemical bases of psychoses or the serotonin hypothesis about mental diseases. New York-London: John Wiley and Sons 1962

    Google Scholar 

  • Youdim, M. B. H., Collins, G. G. S., Sandler, M., Beran Jones A. B., Pare, C. M. B., Nicholson, W. J.: Human brain monoamine oxidase: Multiple forms and selective inhibitors. Nature (Lond.) 236, 225–228 (1972)

    Google Scholar 

  • Zeidenberg, P.: Clinical and metabolic studies with imipramine in man. Amer. J. Psychiat. 127, 1321–1326 (1971)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Anthropologie und Humangenetik der Universität Hedeilberg, Heidelberg, Germany

    Peter Propping & Marijana Kopun

Authors
  1. Peter Propping
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marijana Kopun
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

The work of the authors is supported by the Deutsche Forschungsgemeinschaft.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Propping, P., Kopun, M. Pharmacogenetic aspects of psychoactive drugs: Facts and fancy. Hum Genet 20, 291–320 (1973). https://doi.org/10.1007/BF00273334

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00273334

Keywords

Search

Navigation