Abstract
A new tricyclic antidepressant, doxepin, was evaluated for its ability to block the amine uptake mechanism of the peripheral adrenergic neuron and blood platelet in man. At low doses, there was no evidence of inhibition of the amine pump. However, at moderate doses (200–300 mg/day), necessary for effective antidepressant activity, doxepin was found to inhibit the pressor responses to tyramine and to reduce platelet 5-HT. These studies indicate that doxepin is a less potent inhibitor of the amine pump in the peripheral adrenergic neuron and blood platelet than is DMI or protriptyline. Doxepin, at the antidepressant dose level does alter biogenic amine uptake, an effect consistent with the biogenic amine hypothesis of depression. However, at 300 mg/day, a dose which blocks the pressor response to tyramine, antagonism of the antihypertensive effects of guanethidine and related drugs was demonstrated.
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References
Ayd, F. J. Jr.: A clinical evaluation of doxepin (Sinequan). Dis. nerv. Syst. 30, 396–400 (1969).
—: A clinical appraisal of doxepin. Med. Counterpoint. 1, 25–30 (1969).
Beaubien, J., Ban, T. A., Lehman, H. E., Jarrold, L.: Doxepin in the treatment of psychoneurotic patients. Curr. ther. Res. 12, 192–194 (1970).
Belsasso, G., Tapia, H. L., Grajales, A.: Clinical investigation with doxepin, a new antidepressant. Curr. Ther. Res. 11, 165–168 (1969).
Coleman, J. C.: Severe emotional disturbance associated with physical illness. Psychosomatics 10, 32–35 (1969).
Davis, J. M.: Theories of biological etiology of affective disorders. Int. Rev. Neurobiol. 12, 145–175 (1970).
—, Colburn, R. W., Murphy, D. L., Bunney, W. E. Jr.: A new research tool for the study of brain biogenic amines and psychoactive drugs, scientific proceedings of the annual meeting of the american Psychiatric Association, vol. 124, p. 103 (1968).
—, Goodwin, F. K., Bunney, W. E. Jr., Murphy, D. L., Colburn, R. W.: Effects of ions on uptake of norepinephrine by synaptosomes. Pharmacologist 9, 184 (1967).
Fann, W. E., Janowsky, D. S., Oates, J. A., Davis, J. M.: Interaction of chlorpromazine with guanethidine-produced hypotension. In press. Lancet 1971.
Fielding, J. M.: A double-blind comparative trial of dibenzepin and imipramine. Med. J. Austr. (1969), 614–616.
- Mowbray, M. A., Davies, B.: A preliminary controlled study of doxepin (Sinequan) as an antianxiety drug. Med. J. Aust. 1969, 851–852.
Gallant, D. M., Bishop, M. P., Guerrero-Figueroa, R., Selby, M., Phillips, R.: Doxepin versus diazepam: a controlled evaluation in 100 chronic alcoholic patients. Psychosomatics 10, 37 (1969).
— —, Guerrero-Figueroa, R., Selby, M., Phillips, R.: Doxepin versus diazepam: a controlled evaluation in 100 chronic alcoholic patients. J. Clin. Pharm. 9, 57–65 (1969).
Goldstein, B. J., Pinosky, D. G.: Clinical evaluation of doxepin in anxious depressed outpatients. Psychosomatics 10, 31–38 (1969).
— —: Clinical evaluation of doxepin in anxious depressed outpatients. Curr. Ther. Res. 11, 169–177 (1969).
Gomez-Martinez, I.: Preliminary double-blind clinical trial with a new antidepressive doxepin. Curr. Ther. Res. 10, 116–118 (1968).
Hackett, E., Gold, R. L., Kline, N. S., Winick, L.: Controlled evaluation of psychotropic drugs in a private psychiatric practice. Psychosomatics 8, 162–165 (1967).
—, Kline, N. S.: Antidepressant activity of doxepin and amitriptyline. Psychosomatics 10, 21–24 (1969).
Johnstone, E. E., Claghorn, J. L.: Doxepin vs. chlordiazepoxide: a controlled Comparison in neurotic outpatients. Psychosomatics 10, 38 (1969).
— —: Doxepin vs. chlordiazepoxide: a controlled comparison in neurotic outpatients. Curr. Ther. Res. 10, 514–519 (1968).
Kasich, A. M.: Clinical evaluation of doxepin and diazepam in patients with gastrointestinal disease and anxiety. Psychosomatics 10, 18–20 (1969).
—: A controlled trial of doxepin and diazepam in the treatment of anxiety accompanying gastrointestinal disease. Brit. J. Clin. Pract. 23, 121–122 (1969).
Kingstone, E., Kolivakis, T., Kossatz, I.: Doxepin versus chloridiazepoxide: A double-blind study on anxious outpatients. Curr. Ther. Res. 12, 213–222 (1970).
Krakowski, A.: Activity study of doxepin. Psychosomatics 9, 89–95 (1968).
- The pharmacologic management of mental illness. A scientific exhibit, American psychiatric association annual meeting, May 1969.
—: Biphasic drugs in the treatment of depression with anxiety. Psychosomatics 10, 7–11 (1969).
McLaughlin, B.: Management of psychoneurotic anxiety and depression in outpatients. Psychosomatics 10, 28–31 (1969).
Mitchell, J. A., Arias, L., Oates, J. A.: Antagonism of the antihypertensive action of guanethidine sulfate by desipramine hydrochloride. J. Amer. med. Ass. 202, 973–976 (1967).
—, Cavanaugh, J. H., Arias, L., Oates, J. A.: Guanethidine and related agents: III. Antagonism by drugs which inhibit the norepinephrine pump in man. J. clin. Invest. 49, 1596–1604 (1970a).
— —, Dingell, J. V., Oates, J. A.: Guanethidine and related agents. II. Metabolism by hepatic microsomes and its inhibition by drugs. J. Pharmacol. exp. Ther. 172, 108–114 (1970b).
—, Oates, J. A.: Guanethidine and related agents. I. Mechanism of the selective blockade of adrenergic neurons and its antagonism by drugs. J. Pharmacol. exp. Ther. 172, 100–107 (1970a).
— —: Guanethidine and related agents. I. Mechanism of the selective blockade of adrenergic neurons and its antagonism by drugs. J. Pharmacol. exp. Ther. 172, 100–107 (1970a).
Morgan, D. H., Oates, J. A., Shand, D. G.: Evidence that guanethidine does not block adrenergic nerves by acting as a false transmitter. Brit. J. Pharmacol. 39, 186 (1970).
Murphy, D. L., Colburn, R. W., Davis, J. M., Bunney, W. E.: Imipramine and lithium effects on biogenic amine transport in depressed and manic-depressive patients. Amer. J. Psychiat. 127, 339–345 (1970).
Pettinger, W. A., Soyangco, G., Oates, J. A.: Inhibition of monoamine oxidase in man by furazolidone. Clin. Pharmacol. Ther. 9, 442–447 (1968).
Pitts, N.: The clinical evaluation of doxepin. A new psychotherapeutic agent. Psychosomatics 10, 164–171 (1969).
Pletcher, A.: Metabolism, transfer and storage of 5-HT (5-hydroxytryptamnie) in blood platelets. Brit. J. Pharmacol. 32, 1–16 (1968).
Poldinger, W.: Concerning antidepressive psychotropic therapy in Europe. Psychosomatics 10, 37–38 (1969).
Rickels, K., Perloff, M., Stepansky, W., Dion, H., Case, W., Sapra, E.: Doxepin and diazepam in general practice and hospital clinic neurotic patients: A collaborative controlled study. Psychopharmacologia (Berl.) 15, 265–279 (1969).
Sanger, M. D.: Depression and allergic dermatologic disease. Psychosomatics 10, 25–27 (1969).
—: The treatment of anxiety and depression in the allergic patient. Ann. Allergy 27, 506–510 (1969).
Schildkraut, J. J.: Neuropsychopharmacology and the affective disorders. Boston: Little Brown 1970.
Simeon, J., Spero, M., Fink, M.: Clinical and EEG studies of doxepin. Psychosomatics 10, 14–17 (1969).
—, Spero, M., Nikolovski, O., Fink, M.: A comparison of doxepin and chlordiazepoxide in the therapy of anxiety. Curr. Ther. Res. 12, 201–211 (1970).
Sterlin, C., Ban, T. A., Lehmann, H. E., Jarrold, L.: A comparative evaluation of doxepin and chlordiazepoxide in the treatment of psychoneurotic outpatients. Curr. Ther. Res. 12, 195–200 (1970).
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This investigation was supported in part by Public Health Service Grant Numbers: MH 11468; 2 T01 HE 05545; 1 P11 GM 15431; 5 R01 HE 10842; 5 M01 RR 00095-10; RR 95.
Dr. Oates is a Burroughs-Wellcome Scholar in Clinical Pharmacology.
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Fann, W.E., Cavanaugh, J.H., Kaufmann, J.S. et al. Doxepin: Effects on transport of biogenic amines in man. Psychopharmacologia 22, 111–125 (1971). https://doi.org/10.1007/BF00403619
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DOI: https://doi.org/10.1007/BF00403619