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. 2001 May;26(3):203–220.

Apomorphine and the dopamine hypothesis of schizophrenia: a dilemma?

L Dépatie 1, S Lal 1
PMCID: PMC1408306  PMID: 11394190

Abstract

The dopamine (DA) hypothesis of schizophrenia implicates an enhancement of DA function in the pathophysiology of the disorder, at least in the genesis of positive symptoms. Accordingly, apomorphine, a directly acting DA receptor agonist, should display psychotomimetic properties. A review of the literature shows little or no evidence that apomorphine, in doses that stimulate postsynaptic DA receptors, induces psychosis in non-schizophrenic subjects or a relapse or exacerbation of psychotic symptoms in patients with schizophrenia. After a detailed review of the literature reporting psychotogenic effects of apomorphine in patients with Parkinson's disease, an interpretation of these data is difficult, in part because of several confounding factors, such as the concomitant use of drugs known to induce psychosis and the advanced state of the progressive neurological disorder. In the context of the DA hypothesis of schizophrenia, the limited ability of apomorphine to induce psychosis, in contrast to indirectly acting DA agonists that increase synaptic DA, may be explained by the relatively weak affinity of apomorphine for the D3 receptor compared with DA. Alternatively, enhancement of DA function, though necessary, may be insufficient by itself to induce psychosis.

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Selected References

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  1. Abi-Dargham A., Gil R., Krystal J., Baldwin R. M., Seibyl J. P., Bowers M., van Dyck C. H., Charney D. S., Innis R. B., Laruelle M. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry. 1998 Jun;155(6):761–767. doi: 10.1176/ajp.155.6.761. [DOI] [PubMed] [Google Scholar]
  2. Angrist B., Lee H. K., Gershon S. The antagonism of amphetamine-induced symptomatology by a neuroleptic. Am J Psychiatry. 1974 Jul;131(7):817–819. doi: 10.1176/ajp.131.7.817. [DOI] [PubMed] [Google Scholar]
  3. Angrist B., Rotrosen J., Gershon S. Responses to apomorphine, amphetamine, and neuroleptics in schizophrenic subjects. Psychopharmacology (Berl) 1980 Jan;67(1):31–38. doi: 10.1007/BF00427592. [DOI] [PubMed] [Google Scholar]
  4. Angrist B., Thompson H., Shopsin B., Gershon S. Clinical studies with dopamine-receptor stimulants. Psychopharmacologia. 1975 Nov 21;44(3):273–280. doi: 10.1007/BF00428906. [DOI] [PubMed] [Google Scholar]
  5. Bogerts B., Meertz E., Schönfeldt-Bausch R. Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. Arch Gen Psychiatry. 1985 Aug;42(8):784–791. doi: 10.1001/archpsyc.1985.01790310046006. [DOI] [PubMed] [Google Scholar]
  6. Boyd A. Bromocriptine and psychosis: a literature review. Psychiatr Q. 1995 Spring;66(1):87–95. doi: 10.1007/BF02238717. [DOI] [PubMed] [Google Scholar]
  7. Brambilla F., Scarone S., Ponzano M., Maffei C., Nobile P., Rovere C., Guastalla A. Catecholaminergic drugs in chronic schizophrenia. Neuropsychobiology. 1979;5(4):185–200. doi: 10.1159/000117682. [DOI] [PubMed] [Google Scholar]
  8. Breier A., Su T. P., Saunders R., Carson R. E., Kolachana B. S., de Bartolomeis A., Weinberger D. R., Weisenfeld N., Malhotra A. K., Eckelman W. C. Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2569–2574. doi: 10.1073/pnas.94.6.2569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brem A. S., Bina R. B., Hill N., Alia C., Morris D. J. Effects of licorice derivatives on vascular smooth muscle function. Life Sci. 1997;60(3):207–214. doi: 10.1016/s0024-3205(96)00617-0. [DOI] [PubMed] [Google Scholar]
  10. Broussolle E., Marion M. H., Pollak P. Continuous subcutaneous apomorphine as replacement for levodopa in severe parkinsonian patients after surgery. Lancet. 1992 Oct 3;340(8823):859–860. doi: 10.1016/0140-6736(92)92744-z. [DOI] [PubMed] [Google Scholar]
  11. Butcher L. L., Andén N. E. Effects of apomorphine and amphetamine on schedule-controlled behavior: reversal of tetrabenazine suppression and dopaminergic correlates. Eur J Pharmacol. 1969;6(3):255–264. doi: 10.1016/0014-2999(69)90183-6. [DOI] [PubMed] [Google Scholar]
  12. Carroll B. J., Curtis G. C., Kokmen E. Paradoxical response to dopamine agonists in tardive dyskinesia. Am J Psychiatry. 1977 Jul;134(7):785–789. doi: 10.1176/ajp.134.7.785. [DOI] [PubMed] [Google Scholar]
  13. Cervantes P., Lal S., Smith F., Guyda H. Dopaminergic function in two patients with catalepsy. Acta Psychiatr Scand. 1977 Mar;55(3):214–219. doi: 10.1111/j.1600-0447.1977.tb00164.x. [DOI] [PubMed] [Google Scholar]
  14. Chaudhuri K. R., Clough C. Subcutaneous apomorphine in Parkinson's disease. BMJ. 1998 Feb 28;316(7132):641–641. doi: 10.1136/bmj.316.7132.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chaudhuri K. R., Critchley P., Abbott R. J., Pye I. F., Millac P. A. Subcutaneous apomorphine for on-off oscillations in Parkinson's disease. Lancet. 1988 Nov 26;2(8622):1260–1260. doi: 10.1016/s0140-6736(88)90860-4. [DOI] [PubMed] [Google Scholar]
  16. Colosimo C., Merello M., Albanese A. Clinical usefulness of apomorphine in movement disorders. Clin Neuropharmacol. 1994 Jun;17(3):243–259. doi: 10.1097/00002826-199406000-00004. [DOI] [PubMed] [Google Scholar]
  17. Colzi A., Turner K., Lees A. J. Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1998 May;64(5):573–576. doi: 10.1136/jnnp.64.5.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Corboy D. L., Wagner M. L., Sage J. I. Apomorphine for motor fluctuations and freezing in Parkinson's disease. Ann Pharmacother. 1995 Mar;29(3):282–288. doi: 10.1177/106002809502900310. [DOI] [PubMed] [Google Scholar]
  19. Corsini G. U., Del Zompo M., Manconi S., Cianchetti C., Mangoni A., Gessa G. L. Sedative, hypnotic, and antipsychotic effects of low doses of apomorphine in man. Adv Biochem Psychopharmacol. 1977;16:645–648. [PubMed] [Google Scholar]
  20. Corsini G. U., Pitzalis G. F., Bernardi F., Bocchetta A., Del Zompo M. The use of dopamine agonists in the treatment of schizophrenia. Neuropharmacology. 1981 Dec;20(12B):1309–1313. [PubMed] [Google Scholar]
  21. Costa E., Groppetti A., Naimzada M. K. Effects of amphetamine on the turnover rate of brain catecholamines and motor activity. Br J Pharmacol. 1972 Apr;44(4):742–751. doi: 10.1111/j.1476-5381.1972.tb07312.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Cotzias G. C., Papavasiliou P. S., Fehling C., Kaufman B., Mena I. Similarities between neurologic effects of L-dipa and of apomorphine. N Engl J Med. 1970 Jan 1;282(1):31–33. doi: 10.1056/NEJM197001012820107. [DOI] [PubMed] [Google Scholar]
  23. Cotzias G. C., Papavasiliou P. S., Tolosa E. S., Mendez J. S., Bell-Midura M. Treatment of Parkinson's disease with aporphines. Possible role of growth hormone. N Engl J Med. 1976 Mar 11;294(11):567–572. doi: 10.1056/NEJM197603112941101. [DOI] [PubMed] [Google Scholar]
  24. Courty E., Durif F., Zenut M., Courty P., Lavarenne J. Psychiatric and sexual disorders induced by apomorphine in Parkinson's disease. Clin Neuropharmacol. 1997 Apr;20(2):140–147. doi: 10.1097/00002826-199704000-00005. [DOI] [PubMed] [Google Scholar]
  25. Cutler N. R., Jeste D. V., Karoum F., Wyatt R. J. Low-dose apomorphine reduces serum homovanillic acid concentrations in schizophrenic patients. Life Sci. 1982 Mar 1;30(9):753–756. doi: 10.1016/0024-3205(82)90609-9. [DOI] [PubMed] [Google Scholar]
  26. Davidson M., Kendler K. S., Davis B. M., Horvath T. B., Mohs R. C., Davis K. L. Apomorphine has no effect on plasma homovanillic acid in schizophrenic patients. Psychiatry Res. 1985 Oct;16(2):95–99. doi: 10.1016/0165-1781(85)90002-2. [DOI] [PubMed] [Google Scholar]
  27. Deffond D., Durif F., Tournilhac M. Apomorphine in treatment of Parkinson's disease: comparison between subcutaneous and sublingual routes. J Neurol Neurosurg Psychiatry. 1993 Jan;56(1):101–103. doi: 10.1136/jnnp.56.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Dolan R. J., Fletcher P., Frith C. D., Friston K. J., Frackowiak R. S., Grasby P. M. Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia. Nature. 1995 Nov 9;378(6553):180–182. doi: 10.1038/378180a0. [DOI] [PubMed] [Google Scholar]
  29. Durif F., Deffond D., Dordain G., Tournilhac M. Apomorphine and diphasic dyskinesia. Clin Neuropharmacol. 1994 Feb;17(1):99–102. [PubMed] [Google Scholar]
  30. Durif F., Deffond D., Eschalier A., Tournilhac M. Administration de l'apomorphine par voie sublinguale dans le traitement des fluctuations motrices de la maladie de Parkinson. Rev Neurol (Paris) 1992;148(10):610–614. [PubMed] [Google Scholar]
  31. Esteban Muñoz J., Martí M. J., Marín C., Tolosa E. Long-term treatment with intermitent intranasal or subcutaneous apormorphine in patients with levodopa-related motor fluctuations. Clin Neuropharmacol. 1997 Jun;20(3):245–252. doi: 10.1097/00002826-199706000-00009. [DOI] [PubMed] [Google Scholar]
  32. Ettigi P., Nair N. P., Lal S., Cervantes P., Guyda H. Effect of apomorphine on growth hormone and prolactin secretion in schizophrenic patients, with or without oral dyskinesia, withdrawn from chronic neuroleptic therapy. J Neurol Neurosurg Psychiatry. 1976 Sep;39(9):870–876. doi: 10.1136/jnnp.39.9.870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. FELDMANN H. Le traitement des états anxieux par l'apomorphine; application et résultats cliniques. Rev Med Suisse Romande. 1953 Jun;73(6):431–440. [PubMed] [Google Scholar]
  34. Feldmann H. S. Apomorphine in the treatment of alcohol addiction: neuro-physiological and therapeutic aspects. Psychiatr J Univ Ott. 1983 Mar;8(1):30–37. [PubMed] [Google Scholar]
  35. Fenger H. J., Gudmand-Höyer E., Rasmussen K. A modification of the apomorphine dumping test. Scand J Gastroenterol. 1972;7(8):743–746. doi: 10.3109/00365527209180990. [DOI] [PubMed] [Google Scholar]
  36. Ferrier I. N., Johnstone E. C., Crow T. J. Clinical effects of apomorphine in schizophrenia. Br J Psychiatry. 1984 Apr;144:341–348. doi: 10.1192/bjp.144.4.341. [DOI] [PubMed] [Google Scholar]
  37. Ferris R. M., Tang F. L., Maxwell R. A. A comparison of the capacities of isomers of amphetamine, deoxypipradrol and methylphenidate to inhibit the uptake of tritiated catecholamines into rat cerebral cortex slices, synaptosomal preparations of rat cerebral cortex, hypothalamus and striatum and into adrenergic nerves of rabbit aorta. J Pharmacol Exp Ther. 1972 Jun;181(3):407–416. [PubMed] [Google Scholar]
  38. Frankel J. P., Lees A. J., Kempster P. A., Stern G. M. Subcutaneous apomorphine in the treatment of Parkinson's disease. J Neurol Neurosurg Psychiatry. 1990 Feb;53(2):96–101. doi: 10.1136/jnnp.53.2.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Friedman J. I., Adler D. N., Davis K. L. The role of norepinephrine in the pathophysiology of cognitive disorders: potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer's disease. Biol Psychiatry. 1999 Nov 1;46(9):1243–1252. doi: 10.1016/s0006-3223(99)00232-2. [DOI] [PubMed] [Google Scholar]
  40. GOETHE H. ZUR ANTIMETISCHEN WIRKUNG EINER FLUOR-PHENOTHIAZIN-VERBINDUNG. Arzneimittelforschung. 1964 Aug;14:962–964. [PubMed] [Google Scholar]
  41. Gancher S. T., Nutt J. G., Woodward W. R. Apomorphine infusional therapy in Parkinson's disease: clinical utility and lack of tolerance. Mov Disord. 1995 Jan;10(1):37–43. doi: 10.1002/mds.870100108. [DOI] [PubMed] [Google Scholar]
  42. Gancher S. T., Nutt J. G., Woodward W. R. Time course of tolerance to apomorphine in parkinsonism. Clin Pharmacol Ther. 1992 Nov;52(5):504–510. doi: 10.1038/clpt.1992.178. [DOI] [PubMed] [Google Scholar]
  43. Gancher S. T., Woodward W. R., Boucher B., Nutt J. G. Peripheral pharmacokinetics of apomorphine in humans. Ann Neurol. 1989 Aug;26(2):232–238. doi: 10.1002/ana.410260209. [DOI] [PubMed] [Google Scholar]
  44. Gancher S. T., Woodward W. R., Nutt J. G. Apomorphine tolerance in Parkinson's disease: lack of a dose effect. Clin Neuropharmacol. 1996 Feb;19(1):59–64. doi: 10.1097/00002826-199619010-00004. [DOI] [PubMed] [Google Scholar]
  45. Grandas F., Gancher S. T., Rodriguez M., Lera G., Nutt J. G., Obeso J. A. Differences in the motor response to apomorphine between untreated and fluctuating patients with Parkinson's disease. Clin Neuropharmacol. 1992 Feb;15(1):13–18. doi: 10.1097/00002826-199202000-00002. [DOI] [PubMed] [Google Scholar]
  46. Grandas F., Gancher S., Lera G., Rodriguez M., Woodward W. R., Nutt J., Obeso J. A. Time interval between repeated injections conditions the duration of motor improvement to apomorphine in Parkinson's disease. Neurology. 1992 Jul;42(7):1287–1290. doi: 10.1212/wnl.42.7.1287. [DOI] [PubMed] [Google Scholar]
  47. Grandas F., Obeso J. A. Motor response following repeated apomorphine administration is reduced in Parkinson's disease. Clin Neuropharmacol. 1989 Feb;12(1):14–22. doi: 10.1097/00002826-198902000-00002. [DOI] [PubMed] [Google Scholar]
  48. Griffith J. D., Cavanaugh J., Held J., Oates J. A. Dextroamphetamine. Evaluation of psychomimetic properties in man. Arch Gen Psychiatry. 1972 Feb;26(2):97–100. doi: 10.1001/archpsyc.1972.01750200001001. [DOI] [PubMed] [Google Scholar]
  49. Heinonen E. H., Myllylä V. Safety of selegiline (deprenyl) in the treatment of Parkinson's disease. Drug Saf. 1998 Jul;19(1):11–22. doi: 10.2165/00002018-199819010-00002. [DOI] [PubMed] [Google Scholar]
  50. Hollister L. E., Davis K. L., Berger P. A. Apomorphine in schizophrenia. Commun Psychopharmacol. 1980;4(4):277–281. [PubMed] [Google Scholar]
  51. Hughes A. J., Bishop S., Kleedorfer B., Turjanski N., Fernandez W., Lees A. J., Stern G. M. Subcutaneous apomorphine in Parkinson's disease: response to chronic administration for up to five years. Mov Disord. 1993 Apr;8(2):165–170. doi: 10.1002/mds.870080208. [DOI] [PubMed] [Google Scholar]
  52. Hughes A. J., Bishop S., Stern G. M., Lees A. J. The motor response to repeated apomorphine administration in Parkinson's disease. Clin Neuropharmacol. 1991 Jun;14(3):209–213. doi: 10.1097/00002826-199106000-00003. [DOI] [PubMed] [Google Scholar]
  53. Hughes A. J. Drug treatment of Parkinson's disease in the 1990s. Achievements and future possibilities. Drugs. 1997 Feb;53(2):195–205. doi: 10.2165/00003495-199753020-00002. [DOI] [PubMed] [Google Scholar]
  54. Hughes A. J., Lees A. J., Stern G. M. The motor response to sequential apomorphine in parkinsonian fluctuations. J Neurol Neurosurg Psychiatry. 1991 Apr;54(4):358–360. doi: 10.1136/jnnp.54.4.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Hughes A. J., Webster R., Bovingdon M., Lees A. J., Stern G. M. Sublingual apomorphine in the treatment of Parkinson's disease complicated by motor fluctuations. Clin Neuropharmacol. 1991 Dec;14(6):556–561. doi: 10.1097/00002826-199112000-00008. [DOI] [PubMed] [Google Scholar]
  56. Janowsky D. S., el-Yousel M. K., Davis J. M., Sekerke H. J. Provocation of schizophrenic symptoms by intravenous administration of methylphenidate. Arch Gen Psychiatry. 1973 Feb;28(2):185–191. doi: 10.1001/archpsyc.1973.01750320023004. [DOI] [PubMed] [Google Scholar]
  57. Janssen P. A., Niemegeers C. J., Schellekens K. H., Lenaerts F. M. Is it possible to predict the clinical effects of neuroleptic drugs (major tranquillizers) from animal data? IV. An improved experimental design for measuring the inhibitory effects of neuroleptic drugs on amphetamine-or apomorphine-induced "Cheroing" and "agitation" in rats. Arzneimittelforschung. 1967 Jul;17(7):841–854. [PubMed] [Google Scholar]
  58. Jeste D. V., Cutler N. R., Kaufmann C. A., Karoum F. Low-dose apomorphine and bromocriptine in neuroleptic-induced movement disorders. Biol Psychiatry. 1983 Sep;18(9):1085–1091. [PubMed] [Google Scholar]
  59. Jeste D. V., Zalcman S., Weinberger D. R., Cutler N. R., Bigelow L. B., Kleinman J. E., Rogol A., Wyatt R. J. Apomorphine response and subtyping of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 1983;7(1):83–88. doi: 10.1016/0278-5846(83)90092-1. [DOI] [PubMed] [Google Scholar]
  60. Kempster P. A., Iansek R., Larmour I. Intermittent subcutaneous apomorphine injection treatment for parkinsonian motor oscillations. Aust N Z J Med. 1991 Jun;21(3):314–318. doi: 10.1111/j.1445-5994.1991.tb04696.x. [DOI] [PubMed] [Google Scholar]
  61. Klimek V., Rajkowska G., Luker S. N., Dilley G., Meltzer H. Y., Overholser J. C., Stockmeier C. A., Ordway G. A. Brain noradrenergic receptors in major depression and schizophrenia. Neuropsychopharmacology. 1999 Jul;21(1):69–81. doi: 10.1016/S0893-133X(98)00134-1. [DOI] [PubMed] [Google Scholar]
  62. Lal S., Ackman D., Thavundayil J. X., Kiely M. E., Etienne P. Effect of apomorphine, a dopamine receptor agonist, on penile tumescence in normal subjects. Prog Neuropsychopharmacol Biol Psychiatry. 1984;8(4-6):695–699. doi: 10.1016/0278-5846(84)90040-x. [DOI] [PubMed] [Google Scholar]
  63. Lal S. Apomorphine in the evaluation of dopaminergic function in man. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(2-3):117–164. doi: 10.1016/0278-5846(88)90033-4. [DOI] [PubMed] [Google Scholar]
  64. Lal S., De la Vega C. E. Apomorphine and psychopathology. J Neurol Neurosurg Psychiatry. 1975 Jul;38(7):722–726. doi: 10.1136/jnnp.38.7.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Lal S., De la Vega C. E., Sourkes T. L., Friesen H. G. Effect of apomorphine on growth hormone, prolactin, luteinizing hormone and follicle-stimulating hormone levels in human serum. J Clin Endocrinol Metab. 1973 Nov;37(5):719–724. doi: 10.1210/jcem-37-5-719. [DOI] [PubMed] [Google Scholar]
  66. Lal S., Grassino A., Thavundayil J. X., Dubrovsky B. A simple method for the study of yawning in man induced by the dopamine receptor agonist, apomorphine. Prog Neuropsychopharmacol Biol Psychiatry. 1987;11(2-3):223–228. doi: 10.1016/0278-5846(87)90064-9. [DOI] [PubMed] [Google Scholar]
  67. Lal S., Guyda H., Bikadoroff S. Effect of methysergide and pimozide on apomorphine-induced growth hormone secretion in men. J Clin Endocrinol Metab. 1977 Apr;44(4):766–770. doi: 10.1210/jcem-44-4-766. [DOI] [PubMed] [Google Scholar]
  68. Lal S., Kiely M. E., Thavundayil J. X., Stewart J. D., Assalian P., Ackman C. F. Effect of bromocriptine in patients with apomorphine-responsive erectile impotence: an open study. J Psychiatry Neurosci. 1991 Dec;16(5):262–266. [PMC free article] [PubMed] [Google Scholar]
  69. Lal S., Nair N. P., Thavundayil J. X., Tawar V., Quirion R., Guyda H. Stereospecificity of the dopamine receptor mediating the growth hormone response to apomorphine in man. Short communication. J Neural Transm Gen Sect. 1991;85(2):157–164. doi: 10.1007/BF01244707. [DOI] [PubMed] [Google Scholar]
  70. Lal S., Sourkes T. L., Missala K., Belendiuk G. Effects of aporphine and emetine alkaloids on central dopaminergic mechanisms in rats. Eur J Pharmacol. 1972 Oct;20(1):71–79. doi: 10.1016/0014-2999(72)90217-8. [DOI] [PubMed] [Google Scholar]
  71. Lal S., Sourkes T. L. Ontogeny of stereotyped behaviour induced by apomorphine and amphetamine in the rat. Arch Int Pharmacodyn Ther. 1973 Mar;202(1):171–182. [PubMed] [Google Scholar]
  72. Lal S., Tesfaye Y., Thavundayil J. X., Thompson T. R., Kiely M. E., Nair N. P., Grassino A., Dubrovsky B. Apomorphine: clinical studies on erectile impotence and yawning. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(3-4):329–339. doi: 10.1016/0278-5846(89)90122-x. [DOI] [PubMed] [Google Scholar]
  73. Laruelle M., Abi-Dargham A. Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies. J Psychopharmacol. 1999 Dec;13(4):358–371. doi: 10.1177/026988119901300405. [DOI] [PubMed] [Google Scholar]
  74. Lees A. J. Dopamine agonists in Parkinson's disease: a look at apomorphine. Fundam Clin Pharmacol. 1993;7(3-4):121–128. doi: 10.1111/j.1472-8206.1993.tb00226.x. [DOI] [PubMed] [Google Scholar]
  75. Levy D. L., Smith M., Robinson D., Jody D., Lerner G., Alvir J., Geisler S. H., Szymanski S. R., Gonzalez A., Mayerhoff D. I. Methylphenidate increases thought disorder in recent onset schizophrenics, but not in normal controls. Biol Psychiatry. 1993 Oct 15;34(8):507–514. doi: 10.1016/0006-3223(93)90192-g. [DOI] [PubMed] [Google Scholar]
  76. Levy M. I., Davis B. M., Mohs R. C., Kendler K. S., Mathé A. A., Trigos G., Horvath T. B., Davis K. L. Apomorphine and schizophrenia. Treatment, CSF, and neuroendocrine responses. Arch Gen Psychiatry. 1984 May;41(5):520–524. doi: 10.1001/archpsyc.1984.01790160106014. [DOI] [PubMed] [Google Scholar]
  77. Lieberman A., Goldstein M., Leibowitz M., Neophytides A., Kupersmith M., Pact V., Kleinberg D. Treatment of advanced Parkinson disease with pergolide. Neurology. 1981 Jun;31(6):675–682. doi: 10.1212/wnl.31.6.675. [DOI] [PubMed] [Google Scholar]
  78. Lieberman J. A., Jody D., Alvir J. M., Ashtari M., Levy D. L., Bogerts B., Degreef G., Mayerhoff D. I., Cooper T. Brain morphology, dopamine, and eye-tracking abnormalities in first-episode schizophrenia. Prevalence and clinical correlates. Arch Gen Psychiatry. 1993 May;50(5):357–368. doi: 10.1001/archpsyc.1993.01820170035005. [DOI] [PubMed] [Google Scholar]
  79. Lieberman J. A., Kinon B. J., Loebel A. D. Dopaminergic mechanisms in idiopathic and drug-induced psychoses. Schizophr Bull. 1990;16(1):97–110. doi: 10.1093/schbul/16.1.97. [DOI] [PubMed] [Google Scholar]
  80. Lieberman J. A., Mailman R. B., Duncan G., Sikich L., Chakos M., Nichols D. E., Kraus J. E. Serotonergic basis of antipsychotic drug effects in schizophrenia. Biol Psychiatry. 1998 Dec 1;44(11):1099–1117. doi: 10.1016/s0006-3223(98)00187-5. [DOI] [PubMed] [Google Scholar]
  81. Lieberman J. A., Sheitman B. B., Kinon B. J. Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity. Neuropsychopharmacology. 1997 Oct;17(4):205–229. doi: 10.1016/S0893-133X(97)00045-6. [DOI] [PubMed] [Google Scholar]
  82. MacLean W. C., Jr A comparison of ipecac syrup and apomorphine in the immediate treatment of ingestion of poisons. J Pediatr. 1973 Jan;82(1):121–124. doi: 10.1016/s0022-3476(73)80029-0. [DOI] [PubMed] [Google Scholar]
  83. Martin J. B., Lal S., Tolis G., Friesen H. G. Inhibition by apomorphine of prolactin secretion in patients with elevated serum prolactin. J Clin Endocrinol Metab. 1974 Jul;39(1):180–182. doi: 10.1210/jcem-39-1-180. [DOI] [PubMed] [Google Scholar]
  84. McConaghy N. Subjective and penile plethysmograph responses following aversion-relief and apomorphine aversion therapy for homosexual impulses. Br J Psychiatry. 1969 Jun;115(523):723–730. doi: 10.1192/bjp.115.523.723. [DOI] [PubMed] [Google Scholar]
  85. Meltzer H. Y., Matsubara S., Lee J. C. The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull. 1989;25(3):390–392. [PubMed] [Google Scholar]
  86. Meltzer H. Y. Relevance of dopamine autoreceptors for psychiatry: preclinical and clinical studies. Schizophr Bull. 1980;6(3):456–475. doi: 10.1093/schbul/6.3.456. [DOI] [PubMed] [Google Scholar]
  87. Meltzer H. Y., Stahl S. M. The dopamine hypothesis of schizophrenia: a review. Schizophr Bull. 1976;2(1):19–76. doi: 10.1093/schbul/2.1.19. [DOI] [PubMed] [Google Scholar]
  88. Meltzer H. Y. Treatment of schizophrenia and spectrum disorders: pharmacotherapy, psychosocial treatments, and neurotransmitter interactions. Biol Psychiatry. 1999 Nov 15;46(10):1321–1327. [PubMed] [Google Scholar]
  89. Merello M., Starkstein S., Petracca G., Cataneo E. A., Manes F., Leiguarda R. Drug-induced parkinsonism in schizophrenic patients: motor response and psychiatric changes after acute challenge with L-Dopa and apomorphine. Clin Neuropharmacol. 1996 Oct;19(5):439–443. doi: 10.1097/00002826-199619050-00007. [DOI] [PubMed] [Google Scholar]
  90. Montastruc J. L., Rascol O., Senard J. M., Houin G., Rascol A. Sublingual apomorphine: a new pharmacological approach in Parkinson's disease? J Neural Transm Suppl. 1995;45:157–161. [PubMed] [Google Scholar]
  91. Muhiddin K. A., Roche M. T., Pearce V. R. Subcutaneous apomorphine infusion in Parkinson's disease: does it have a role? Postgrad Med J. 1994 May;70(823):344–346. doi: 10.1136/pgmj.70.823.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Murphy D. L. Mental effects of L-dopa. Annu Rev Med. 1973;24:209–216. doi: 10.1146/annurev.me.24.020173.001233. [DOI] [PubMed] [Google Scholar]
  93. Nair N. P., Lal S., Iskandar H. I., Etienne P., Wood P. L., Guyda H. Effect of sulpiride, an atypical neuroleptic, on apomorphine-induced growth hormone secretion. Brain Res Bull. 1982 Jun;8(6):587–591. doi: 10.1016/0361-9230(82)90085-5. [DOI] [PubMed] [Google Scholar]
  94. Obeso J. A., Grandas F., Vaamonde J., Rosario Luguin M., Martínez-Lage J. M. Apomorphine infusion for motor fluctuations in Parkinson's disease. Lancet. 1987 Jun 13;1(8546):1376–1377. doi: 10.1016/s0140-6736(87)90679-9. [DOI] [PubMed] [Google Scholar]
  95. Olney J. W., Farber N. B. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry. 1995 Dec;52(12):998–1007. doi: 10.1001/archpsyc.1995.03950240016004. [DOI] [PubMed] [Google Scholar]
  96. Ostergaard L., Werdelin L., Odin P., Lindvall O., Dupont E., Christensen P. B., Boisen E., Jensen N. B., Ingwersen S. H., Schmiegelow M. Pen injected apomorphine against off phenomena in late Parkinson's disease: a double blind, placebo controlled study. J Neurol Neurosurg Psychiatry. 1995 Jun;58(6):681–687. doi: 10.1136/jnnp.58.6.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Peyser CE, Naimark D, Zuniga R, Jeste DV. Psychoses in Parkinson's Disease. Semin Clin Neuropsychiatry. 1998 Jan;3(1):41–50. [PubMed] [Google Scholar]
  98. Pietz K., Hagell P., Odin P. Subcutaneous apomorphine in late stage Parkinson's disease: a long term follow up. J Neurol Neurosurg Psychiatry. 1998 Nov;65(5):709–716. doi: 10.1136/jnnp.65.5.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Poewe W., Kleedorfer B., Gerstenbrand F., Oertel W. Subcutaneous apomorphine in Parkinson's disease. Lancet. 1988 Apr 23;1(8591):943–943. doi: 10.1016/s0140-6736(88)91755-2. [DOI] [PubMed] [Google Scholar]
  100. Poewe W., Kleedorfer B., Wagner M., Benke T., Gasser T., Oertel W. Side-effects of subcutaneous apomorphine in Parkinson's disease. Lancet. 1989 May 13;1(8646):1084–1085. doi: 10.1016/s0140-6736(89)92487-2. [DOI] [PubMed] [Google Scholar]
  101. Poewe W., Kleedorfer B., Wagner M., Bösch S., Schelosky L. Continuous subcutaneous apomorphine infusions for fluctuating Parkinson's disease. Long-term follow-up in 18 patients. Adv Neurol. 1993;60:656–659. [PubMed] [Google Scholar]
  102. Pollak P., Benabid A. L., Limousin P., Gervason C. L., Jeanneau-Nicolle E. External and implanted pumps for apomorphine infusion in parkinsonism. Acta Neurochir Suppl (Wien) 1993;58:48–52. doi: 10.1007/978-3-7091-9297-9_10. [DOI] [PubMed] [Google Scholar]
  103. Pollak P., Champay A. S., Gaio J. M., Hommel M., Benabid A. L., Perret J. Administration sous-cutanée d'apomorphine dans les fluctuations motrices de la maladie de Parkinson. Rev Neurol (Paris) 1990;146(2):116–122. [PubMed] [Google Scholar]
  104. Pollak P., Champay A. S., Hommel M., Perret J. E., Benabid A. L. Subcutaneous apomorphine in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1989 Apr;52(4):544–544. doi: 10.1136/jnnp.52.4.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Quesney L. F., Andermann F., Lal S., Prelevic S. Transient abolition of generalized photosensitive epileptic discharge in humans by apomorphine, a dopamine-receptor agonist. Neurology. 1980 Nov;30(11):1169–1174. doi: 10.1212/wnl.30.11.1169. [DOI] [PubMed] [Google Scholar]
  106. Ray-Chaudhuri K., Abbott R. J., Millac P. A. Subcutaneous apomorphine for parkinsonian patients with psychiatric side effects on oral treatment. J Neurol Neurosurg Psychiatry. 1991 Apr;54(4):372–373. doi: 10.1136/jnnp.54.4.372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Reid W. D. Turnover rate of brain 5-hydroxytryptamine increased by D-amphetamine. Br J Pharmacol. 1970 Nov;40(3):483–491. doi: 10.1111/j.1476-5381.1970.tb10629.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Ruggieri S., Stocchi F., Carta A., Agnoli A. Side-effects of subcutaneous apomorphine in Parkinson's disease. Lancet. 1989 Mar 11;1(8637):566–566. doi: 10.1016/s0140-6736(89)90116-5. [DOI] [PubMed] [Google Scholar]
  109. SCHWAB R. S., AMADOR L. V., LETTVIN J. Y. Apomorphine in Parkinson's disease. Trans Am Neurol Assoc. 1951;56:251–253. [PubMed] [Google Scholar]
  110. Sanchez-Ramos J. R., Ortoll R., Paulson G. W. Visual hallucinations associated with Parkinson disease. Arch Neurol. 1996 Dec;53(12):1265–1268. doi: 10.1001/archneur.1996.00550120077019. [DOI] [PubMed] [Google Scholar]
  111. Sato M., Numachi Y., Hamamura T. Relapse of paranoid psychotic state in methamphetamine model of schizophrenia. Schizophr Bull. 1992;18(1):115–122. doi: 10.1093/schbul/18.1.115. [DOI] [PubMed] [Google Scholar]
  112. Scarzella L., Delsedime M., Ferrero B., Giangrandi C., Priano L., Rizzone M., Bergamasco B. Apomorphine SC treatment in parkinsonian patients with long-term L-dopa syndrome during L-dopa drug holiday. J Neural Transm Suppl. 1995;45:163–170. [PubMed] [Google Scholar]
  113. Scheel-Krüger J. Comparative studies of various amphetamine analogues demonstrating different interactions with the metabolism of the catecholamines in the brain. Eur J Pharmacol. 1971;14(1):47–59. doi: 10.1016/0014-2999(71)90121-x. [DOI] [PubMed] [Google Scholar]
  114. Schlatter E. K., Lal S. Treatment of alcoholism with Dent's oral apomorphine method. Q J Stud Alcohol. 1972 Jun;33(2):430–436. [PubMed] [Google Scholar]
  115. Schneider C. Behavioural effects of some morphine antagonists and hallucinogens in the rat. Nature. 1968 Nov 9;220(5167):586–587. doi: 10.1038/220586a0. [DOI] [PubMed] [Google Scholar]
  116. Seeman P. Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse. 1987;1(2):133–152. doi: 10.1002/syn.890010203. [DOI] [PubMed] [Google Scholar]
  117. Seeman P., Tallerico T. Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors. Mol Psychiatry. 1998 Mar;3(2):123–134. doi: 10.1038/sj.mp.4000336. [DOI] [PubMed] [Google Scholar]
  118. Seeman P., Tallerico T. Rapid release of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. Am J Psychiatry. 1999 Jun;156(6):876–884. doi: 10.1176/ajp.156.6.876. [DOI] [PubMed] [Google Scholar]
  119. Seeman P., Van Tol H. H. Dopamine receptor pharmacology. Trends Pharmacol Sci. 1994 Jul;15(7):264–270. doi: 10.1016/0165-6147(94)90323-9. [DOI] [PubMed] [Google Scholar]
  120. Shields K. G., Ballinger C. M., Hathaway B. N. Antiemetic effectiveness of haloperidol in human volunteers challenged with apomorphine. Anesth Analg. 1971 Nov-Dec;50(6):1017–1024. doi: 10.1213/00000539-197150060-00023. [DOI] [PubMed] [Google Scholar]
  121. Simpkin D. M., Milner R., Snell A. P. Continuous subcutaneous apomorphine infusion in Parkinson's disease. Med J Aust. 1992 Jun 15;156(12):883–884. [PubMed] [Google Scholar]
  122. Smith R. C., Tamminga C., Davis J. M. Effect of apomorphine on schizophrenic symptoms. J Neural Transm. 1977;40(2):171–176. doi: 10.1007/BF01250567. [DOI] [PubMed] [Google Scholar]
  123. Smythies J. R., Johnston V. S., Bradley R. J., Benington F., Morin R. D., Clark L. C. Some new behaviour-disrupting amphetamines and their significance. Nature. 1967 Oct 14;216(5111):128–129. doi: 10.1038/216128a0. [DOI] [PubMed] [Google Scholar]
  124. Sokoloff P., Giros B., Martres M. P., Bouthenet M. L., Schwartz J. C. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. 1990 Sep 13;347(6289):146–151. doi: 10.1038/347146a0. [DOI] [PubMed] [Google Scholar]
  125. Steiger M. J., Quinn N. P., Marsden C. D. The clinical use of apomorphine in Parkinson's disease. J Neurol. 1992 Aug;239(7):389–393. doi: 10.1007/BF00812157. [DOI] [PubMed] [Google Scholar]
  126. Stibe C. M., Lees A. J., Kempster P. A., Stern G. M. Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet. 1988 Feb 20;1(8582):403–406. doi: 10.1016/s0140-6736(88)91193-2. [DOI] [PubMed] [Google Scholar]
  127. Stibe C., Lees A., Stern G. Subcutaneous infusion of apomorphine and lisuride in the treatment of parkinsonian on-off fluctuations. Lancet. 1987 Apr 11;1(8537):871–871. doi: 10.1016/s0140-6736(87)91660-6. [DOI] [PubMed] [Google Scholar]
  128. Syvälahti E. K., Säkö E., Scheinin M., Pihlajamäki K., Hietala J. Effects of intravenous and subcutaneous administration of apomorphine on the clinical symptoms of chronic schizophrenics. Br J Psychiatry. 1986 Feb;148:204–208. doi: 10.1192/bjp.148.2.204. [DOI] [PubMed] [Google Scholar]
  129. Tamminga C. A., Gotts M. D., Thaker G. K., Alphs L. D., Foster N. L. Dopamine agonist treatment of schizophrenia with N-propylnorapomorphine. Arch Gen Psychiatry. 1986 Apr;43(4):398–402. doi: 10.1001/archpsyc.1986.01800040108015. [DOI] [PubMed] [Google Scholar]
  130. Tamminga C. A., Schaffer M. H., Smith R. C., Davis J. M. Schizophrenic symptoms improve with apomorphine. Science. 1978 May 5;200(4341):567–568. doi: 10.1126/science.347574. [DOI] [PubMed] [Google Scholar]
  131. Tsang D., Lal S. Effect of monoamine receptor agonists and antagonists on cyclic AMP accumulation in human cerebral cortex slices. Can J Physiol Pharmacol. 1977 Dec;55(6):1263–1269. doi: 10.1139/y77-172. [DOI] [PubMed] [Google Scholar]
  132. Vaamonde J., Luquin M. R., Obeso J. A. Subcutaneous lisuride infusion in Parkinson's disease. Response to chronic administration in 34 patients. Brain. 1991 Feb;114(Pt 1B):601–617. doi: 10.1093/brain/114.1.601. [DOI] [PubMed] [Google Scholar]
  133. WHITE R. R. The use of apomorphine with scopolamine in labor. Am J Obstet Gynecol. 1952 Jul;64(1):91–100. doi: 10.1016/s0002-9378(16)38738-5. [DOI] [PubMed] [Google Scholar]
  134. Wenning G. K., Bösch S., Luginger E., Wagner M., Poewe W. Effects of long-term, continuous subcutaneous apomorphine infusions on motor complications in advanced Parkinson's disease. Adv Neurol. 1999;80:545–548. [PubMed] [Google Scholar]
  135. Wilcox J. Psychoactive properties of amantadine. J Psychoactive Drugs. 1985 Jan-Mar;17(1):51–53. doi: 10.1080/02791072.1985.10472319. [DOI] [PubMed] [Google Scholar]
  136. van Laar T., van der Geest R., Danhof M., Boddé H. E., Goossens P. H., Roos R. A. Stepwise intravenous infusion of apomorphine to determine the therapeutic window in patients with Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):152–158. [PubMed] [Google Scholar]

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