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Apomorphine and Schizophrenia: Treatment, CSF, and Neuroendocrine Responses

Apomorphine and Schizophrenia: Treatment, CSF, and Neuroendocrine Responses Abstract • Previous studies have variably reported the efficacy of apomorphine in treatment of schizophrenia and tardive dyskinesia. Stimulation of dopamine neuron autoreceptors is the presumed mode of action. Low-dose apomorphine (0.75 mg subcutaneously) and placebo were administered to 25 male schizophrenics to evaluate the drug's effect on psychotic and tardive dyskinetic symptoms. No significant improvement or deterioration was seen. Concomitant measurements of plasma prolactin and growth hormone levels and CSF homovanillic acid level indicated that the dose used was centrally active. These results indicate that an active though nonsedating dose of apomorphine does not ameliorate symptoms of schizophrenia or tardive dyskinesia. References 1. Roth RH: Dopamine autoreceptors: Pharmacology, function and comparison with post-synaptic dopamine receptors . Commun Psychopharmacol 1979;3:429-445. 2. Aghajanian GK, Bunney BS: Dopamine 'autoreceptors': Pharmacological characterization by microiontophoretic single cell recording studies . Naunyn Schmiedebergs Arch Pharmacol 1976;297:1-7.Crossref 3. Siggins GR, Hoffer BJ, Ungestedt U: Electrophysiological evidence for involvement of cyclic adenosine monophosphate in dopamine responses of caudate neurons . Life Sci 1974;16:779-792.Crossref 4. Martes MP, Costentin J, Baudry M, Marcais H, Protais P, Schwartz JC: Long-term changes in the sensitivity of pre- and postsynaptic dopamine receptors in mouse striatum evidenced by behavioral and biochemical studies . Brain Res 1977;136:319-337.Crossref 5. Skirboll LR, Grace AA, Bunney BS: Dopamine auto- and post-synaptic receptors: Electrophysiological evidence for differential sensitivity to dopamine agonists . Science 1979;206:80-82.Crossref 6. Carlsson A: Does dopamine have a role in schizophrenia? Biol Psychiatry 1978;13:3-21. 7. Klawans HL: The pharmacology of tardive dyskinesias . Am J Psychiatry 1973;130:82-86. 8. Douglas CJ: Apomorphine as a hypnotic . NY Med J 1900;71:376-378. 9. Bleuler E: Dementia Praecox, or the Group of Schizophrenias . New York, International Universities Press, 1950, p 486. 10. Feldman F, Susselman S, Barrera SE: A note on apomorphine as a sedative . Am J Psychiatry 1945;102:403-405. 11. Smith RC, Tamminga C, Davis JM: Effect of apomorphine on schizophrenic symptoms . J Neural Transm 1977;40:171-176.Crossref 12. Corsini GU, DelZompo M, Manconi S, Cianchetti C, Mangoni A, Gessa GL: Sedative, hypnotic, and antipsychotic effects of low doses of apomorphine in man , in Costa E, Gessa GL (eds): Advances in Biochemical Pharmacology . New York, Raven Press, 1977, vol 16, pp 645-648. 13. Tamminga CA, Schaffer MH, Smith RC, Davis JM: Schizophrenic symptoms improve with apomorphine . Science 1978;200:567-568.Crossref 14. Hollister LE, Davis KL, Berger PA: Apomorphine in schizophrenia . Commun Psychopharmacol 1980;4:277-281. 15. Meltzer HY: Relevance of dopamine autoreceptors for psychiatry: Preclinical and clinical studies . Schizophr Bull 1980;6:456-475.Crossref 16. Ferrier IN: Clinical and hormonal effects of apomorphine (APO) in acute and chronic schizophrenia . Br J Psychiatry 1982;140:204. 17. Cutler NR, Jeste DV, Karoum F, Wyatt RJ: Low-dose apomorphine reduces serum homovanillic acid concentrations in schizophrenic patients . Life Sci 1982;30:753-756.Crossref 18. Tarsy D, Gardos G, Cole JO: The effect of dopamine agonists in tardive dyskinesia . Neurology 1979;29:604-607.Crossref 19. Carroll BJ, Curtis GC, Kokmen E: Paradoxical response to dopamine agonists in tardive dyskinesia . Am J Psychiatry 1977;134:785-789. 20. Smith RC, Tamminga CA, Harasyti J, Pandey GN, Davis JM: Effects of dopamine agonists in tardive dyskinesia . Am J Psychiatry 1977;134:763-768. 21. Tolosa ES: Modification of tardive dyskinesia and spasmodic torticollis by apomorphine . Arch Neurol 1978;35:459-462.Crossref 22. Jus K, Jus A, Villeneuve A: Polygraphic profile of oral tardive dyskinesia and of rabbit syndrome . Dis Nerv System 1973;34:27-32. 23. Lal S, de la Vega EE, Sourkes TL, Friesen HG: Effect of apomorphine on growth hormone, prolactin, leutinizing hormone, and follicle stimulating hormone in human serum . J Clin Endocrinol Metabol 1973;37:719-724.Crossref 24. Westerink BHC, Korf J: Influence of drugs on striatal and limbic homovanillic acid concentration in the rat brain . Eur J Pharmacol 1975;33:31-40.Crossref 25. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria (RDC)for a Selected Group of Functional Disorders , ed 3. New York, State Psychiatric Institute, 1978. 26. Endicott J, Spitzer RL: A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia . Arch Gen Psychiatry 1978;35:837-844.Crossref 27. Feighner JP, Robins E, Guze SB, Woodruff RA, Winokur G, Munoz R: Diagnostic criteria for use in psychiatric research . Arch Gen Psychiatry 1972;26:57-63.Crossref 28. Overall JE, Gorham DR: The Brief Psychiatric Rating Scale . Psychol Rep 1962;10:799-812.Crossref 29. Strauss J, Carpenter W: The prediction in outcome in schizophrenia: I. Characteristics of outcome . Arch Gen Psychiatry 1972;27:739-746.Crossref 30. Guy W: ECDEU Assessment Manual for Psychopharmacology . Dept of Health, Education, and Welfare, 1976, pp 534-537. 31. Anderson GM, Young JG, Cohen DJ: Rapid liquid chromatography determination of tryptophan, tyrosine, 5-hydroxy-indole acetic acid, and homovanillic acid in cerebrospinal fluid . J Chromatogr 1979;164:501-505.Crossref 32. Rothpearl AB, Mohs RC, Davis KL: Statistical power in biological psychiatry . Psychiatr Res 1981;5:257-266.Crossref 33. Davis KL, Hollister LE, Mathe AA, Davis BM, Rothpearl A, Faull FK, Hsieh J Y-K, Barchas JD, Berger PA: Neuroendocrine and neurochemical measurements in depression . Am J Psychiatry 1981;138:1555-1561. 34. Faull FK, Kraemer HC, Barchas JD, Berger PA: Clinical application of the probenecid test for measurement of monoamine turnover in the CNS . Biol Psychiatry 1981;16:879-899. 35. Bannon MJ, Michaud RL, Roth RH: Mesocortical dopamine neurons: Lack of autoreceptors modulating dopamine synthesis . Molec Pharmacol 1981;19:270-275. 36. Bunney BS, Aghajanian GK: Mesolimbic and mesocortical dopaminergic systems: Physiology and pharmacology , in Lipton MA, Di Mascio A, Killan KF (eds): Psychopharmacology: A Generation of Progress . New York, Raven Press, 1978, pp 159-169. 37. Melzacka M, Wisyniowska G, Weadyslawa D, Ventulani J: Behavioral effects and cerebral pharmacokinetics of apomorphine in the rat: Dependence upon the route of administration . Pol J Pharmacol Pharm 1979;31:309-317. 38. Portig PJ, Vogt M: Release into the cerebral ventricles of substances with possible transmitter function in the caudate nucleus . J Physiol 1969;204:687-715. 39. Nakano S, Hara C, Ogawa N: Circadian rhythm of apomorphine induced stereotypy in rats . Pharmacol Biochem Behav 1980;12:459-461.Crossref 40. Naber D, Wirz-Justice A, Kafka MS, Wehr TA: Dopamine receptor binding in rat striatum: Ultradian rhythm and its modification by chronic imipramine . Psychopharmacology 1980;68:1-5.Crossref 41. Perlow MJ, Gordon EK, Ebert ME, Hoffman HJ, Chase TN: The circadian variation in dopamine metabolism in the subhuman primate . J Neurochem 1977;28:1381-1383.Crossref 42. Meltzer HY: Relevance of dopamine autoreceptors for psychiatry: Preclinical and clinical studies . Schizophr Bull 1980;6:456-475.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Apomorphine and Schizophrenia: Treatment, CSF, and Neuroendocrine Responses

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References (44)

Publisher
American Medical Association
Copyright
Copyright © 1984 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1984.01790160106014
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Abstract

Abstract • Previous studies have variably reported the efficacy of apomorphine in treatment of schizophrenia and tardive dyskinesia. Stimulation of dopamine neuron autoreceptors is the presumed mode of action. Low-dose apomorphine (0.75 mg subcutaneously) and placebo were administered to 25 male schizophrenics to evaluate the drug's effect on psychotic and tardive dyskinetic symptoms. No significant improvement or deterioration was seen. Concomitant measurements of plasma prolactin and growth hormone levels and CSF homovanillic acid level indicated that the dose used was centrally active. These results indicate that an active though nonsedating dose of apomorphine does not ameliorate symptoms of schizophrenia or tardive dyskinesia. References 1. Roth RH: Dopamine autoreceptors: Pharmacology, function and comparison with post-synaptic dopamine receptors . Commun Psychopharmacol 1979;3:429-445. 2. Aghajanian GK, Bunney BS: Dopamine 'autoreceptors': Pharmacological characterization by microiontophoretic single cell recording studies . Naunyn Schmiedebergs Arch Pharmacol 1976;297:1-7.Crossref 3. Siggins GR, Hoffer BJ, Ungestedt U: Electrophysiological evidence for involvement of cyclic adenosine monophosphate in dopamine responses of caudate neurons . Life Sci 1974;16:779-792.Crossref 4. Martes MP, Costentin J, Baudry M, Marcais H, Protais P, Schwartz JC: Long-term changes in the sensitivity of pre- and postsynaptic dopamine receptors in mouse striatum evidenced by behavioral and biochemical studies . Brain Res 1977;136:319-337.Crossref 5. Skirboll LR, Grace AA, Bunney BS: Dopamine auto- and post-synaptic receptors: Electrophysiological evidence for differential sensitivity to dopamine agonists . Science 1979;206:80-82.Crossref 6. Carlsson A: Does dopamine have a role in schizophrenia? Biol Psychiatry 1978;13:3-21. 7. Klawans HL: The pharmacology of tardive dyskinesias . Am J Psychiatry 1973;130:82-86. 8. Douglas CJ: Apomorphine as a hypnotic . NY Med J 1900;71:376-378. 9. Bleuler E: Dementia Praecox, or the Group of Schizophrenias . New York, International Universities Press, 1950, p 486. 10. Feldman F, Susselman S, Barrera SE: A note on apomorphine as a sedative . Am J Psychiatry 1945;102:403-405. 11. Smith RC, Tamminga C, Davis JM: Effect of apomorphine on schizophrenic symptoms . J Neural Transm 1977;40:171-176.Crossref 12. Corsini GU, DelZompo M, Manconi S, Cianchetti C, Mangoni A, Gessa GL: Sedative, hypnotic, and antipsychotic effects of low doses of apomorphine in man , in Costa E, Gessa GL (eds): Advances in Biochemical Pharmacology . New York, Raven Press, 1977, vol 16, pp 645-648. 13. Tamminga CA, Schaffer MH, Smith RC, Davis JM: Schizophrenic symptoms improve with apomorphine . Science 1978;200:567-568.Crossref 14. Hollister LE, Davis KL, Berger PA: Apomorphine in schizophrenia . Commun Psychopharmacol 1980;4:277-281. 15. Meltzer HY: Relevance of dopamine autoreceptors for psychiatry: Preclinical and clinical studies . Schizophr Bull 1980;6:456-475.Crossref 16. Ferrier IN: Clinical and hormonal effects of apomorphine (APO) in acute and chronic schizophrenia . Br J Psychiatry 1982;140:204. 17. Cutler NR, Jeste DV, Karoum F, Wyatt RJ: Low-dose apomorphine reduces serum homovanillic acid concentrations in schizophrenic patients . Life Sci 1982;30:753-756.Crossref 18. Tarsy D, Gardos G, Cole JO: The effect of dopamine agonists in tardive dyskinesia . Neurology 1979;29:604-607.Crossref 19. Carroll BJ, Curtis GC, Kokmen E: Paradoxical response to dopamine agonists in tardive dyskinesia . Am J Psychiatry 1977;134:785-789. 20. Smith RC, Tamminga CA, Harasyti J, Pandey GN, Davis JM: Effects of dopamine agonists in tardive dyskinesia . Am J Psychiatry 1977;134:763-768. 21. Tolosa ES: Modification of tardive dyskinesia and spasmodic torticollis by apomorphine . Arch Neurol 1978;35:459-462.Crossref 22. Jus K, Jus A, Villeneuve A: Polygraphic profile of oral tardive dyskinesia and of rabbit syndrome . Dis Nerv System 1973;34:27-32. 23. Lal S, de la Vega EE, Sourkes TL, Friesen HG: Effect of apomorphine on growth hormone, prolactin, leutinizing hormone, and follicle stimulating hormone in human serum . J Clin Endocrinol Metabol 1973;37:719-724.Crossref 24. Westerink BHC, Korf J: Influence of drugs on striatal and limbic homovanillic acid concentration in the rat brain . Eur J Pharmacol 1975;33:31-40.Crossref 25. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria (RDC)for a Selected Group of Functional Disorders , ed 3. New York, State Psychiatric Institute, 1978. 26. Endicott J, Spitzer RL: A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia . Arch Gen Psychiatry 1978;35:837-844.Crossref 27. Feighner JP, Robins E, Guze SB, Woodruff RA, Winokur G, Munoz R: Diagnostic criteria for use in psychiatric research . Arch Gen Psychiatry 1972;26:57-63.Crossref 28. Overall JE, Gorham DR: The Brief Psychiatric Rating Scale . Psychol Rep 1962;10:799-812.Crossref 29. Strauss J, Carpenter W: The prediction in outcome in schizophrenia: I. Characteristics of outcome . Arch Gen Psychiatry 1972;27:739-746.Crossref 30. Guy W: ECDEU Assessment Manual for Psychopharmacology . Dept of Health, Education, and Welfare, 1976, pp 534-537. 31. Anderson GM, Young JG, Cohen DJ: Rapid liquid chromatography determination of tryptophan, tyrosine, 5-hydroxy-indole acetic acid, and homovanillic acid in cerebrospinal fluid . J Chromatogr 1979;164:501-505.Crossref 32. Rothpearl AB, Mohs RC, Davis KL: Statistical power in biological psychiatry . Psychiatr Res 1981;5:257-266.Crossref 33. Davis KL, Hollister LE, Mathe AA, Davis BM, Rothpearl A, Faull FK, Hsieh J Y-K, Barchas JD, Berger PA: Neuroendocrine and neurochemical measurements in depression . Am J Psychiatry 1981;138:1555-1561. 34. Faull FK, Kraemer HC, Barchas JD, Berger PA: Clinical application of the probenecid test for measurement of monoamine turnover in the CNS . Biol Psychiatry 1981;16:879-899. 35. Bannon MJ, Michaud RL, Roth RH: Mesocortical dopamine neurons: Lack of autoreceptors modulating dopamine synthesis . Molec Pharmacol 1981;19:270-275. 36. Bunney BS, Aghajanian GK: Mesolimbic and mesocortical dopaminergic systems: Physiology and pharmacology , in Lipton MA, Di Mascio A, Killan KF (eds): Psychopharmacology: A Generation of Progress . New York, Raven Press, 1978, pp 159-169. 37. Melzacka M, Wisyniowska G, Weadyslawa D, Ventulani J: Behavioral effects and cerebral pharmacokinetics of apomorphine in the rat: Dependence upon the route of administration . Pol J Pharmacol Pharm 1979;31:309-317. 38. Portig PJ, Vogt M: Release into the cerebral ventricles of substances with possible transmitter function in the caudate nucleus . J Physiol 1969;204:687-715. 39. Nakano S, Hara C, Ogawa N: Circadian rhythm of apomorphine induced stereotypy in rats . Pharmacol Biochem Behav 1980;12:459-461.Crossref 40. Naber D, Wirz-Justice A, Kafka MS, Wehr TA: Dopamine receptor binding in rat striatum: Ultradian rhythm and its modification by chronic imipramine . Psychopharmacology 1980;68:1-5.Crossref 41. Perlow MJ, Gordon EK, Ebert ME, Hoffman HJ, Chase TN: The circadian variation in dopamine metabolism in the subhuman primate . J Neurochem 1977;28:1381-1383.Crossref 42. Meltzer HY: Relevance of dopamine autoreceptors for psychiatry: Preclinical and clinical studies . Schizophr Bull 1980;6:456-475.Crossref

Journal

Archives of General Psychiatry – American Medical Association

Published: May 1, 1984

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