Hostname: page-component-76fb5796d-2lccl Total loading time: 0 Render date: 2024-04-25T08:51:45.731Z Has data issue: false hasContentIssue false
  • English
  • Français

Understanding the Mechanism of Action of Atypical Antipsychotic Drugs

A Review of Compounds in Use and Development

Published online by Cambridge University Press:  06 August 2018

Jeffrey A. Lieberman
Jeffrey A. Lieberman*
Affiliation:
Hillside Hospital, Division of Long Island Jewish Medical Center, Albert Einstein College of Medicine, PO Box 38, Glen Oaks, NY 11004, USA
Get access Rights & Permissions [Opens in a new window]

Abstract

The thrust of development of new antipsychotic drugs has been to identify new compounds that have enhanced antipsychotic efficacy and have lesser side-effects than standard neuroleptic compounds. Drug development strategies no longer concentrate on D2 receptor antagonism but aim to produce novel compounds. The following have been pursued: (a) selective dopamine receptor antagonists; (b) serotonin receptor agonists and antagonists (5-HT1a,e, 5-HT2, 5-HT3) or mixed 5-HT2 - D2 receptor antagonist; (c) selective dopamine agonists or partial agonists; and (d) sigma-site and excitatory amino-acid antagonists. Such compounds are at various stages of development. The only drug which has truly distinguished itself as ‘atypical’ is clozapine. Its mechanism of action is unknown and the search for it, in large part, has been the impetus for development of the compounds listed above.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 163 , Issue S22: The Psychopharmacology of Schizophrenia , December 1993 , pp. 7 - 18
Copyright
Copyright © 1993 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Anderson, P. H. & Braestrup, C. (1986) Evidence for different states of the dopamine D1 receptor; clozapine and fluperlapine may preferentially label an adenylate cyclase-coupled state of the D1 receptor. Journal of Neurochemistry, 47, 1822–1831.Google Scholar
Awad, A. G., Lapierre, Y. D., Nair, N. P. V., et al (1990) Remoxipride – a selective dopamine D2 antagonist in the treatment of acute schizophrenia: a Canadian multicentre clinical trial. Schizophrenia Research, 3, 45.Google Scholar
Ayd, F. J. Jr (1961) A survey of drug-induced extrapyramidal reactions. Journal of American Medical Association, 175, 1054–1060.Google Scholar
Baldessarini, R. J. (1985) Antipsychotic agents. In Chemotherapy in Psychiatry: Principles and Practice, pp. 14–92. Cambridge, MA: Harvard University Press.Google Scholar
Baldessarini, R. J. & Frankenburg, F. R. (1991) Clozapine a novel antipsychotic agent. New England Journal of Medicine, 324, 746–754.Google Scholar
Bartholini, G. (1976) Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. Journal of Pharmacy and Pharmacology, 28, 429–433.Google Scholar
Benkert, O., Wetzel, H. & Wiedemann, K. (1990) Dopamine autoreceptor agonists in the treatment of positive and negative schizophrenia. In Clinical Neuropharmacology: Proceedings from the 17th CINP Congress (eds Yamachita, I., Toru, M. & Coppen, A.J.), pp. 178–179. New York: Raven Press.Google Scholar
Bersani, G., Grispini, A., Marini, S., et al (1986) Neuroleptic-induced extrapyramidal side effects: clinical perspectives with ritanserin (R 55667), a new selective 5HT2 receptor blocking agent. Current Therapeutic Research, 40, 492–499.Google Scholar
Blaha, C. D. & Lane, R. F. (1987) Chronic treatment with classical and atypical antipsychotic drugs differentially decrease dopamine release in striatum and nucleus accumbens in vivo. Neuroscience Letters, 78, 188–204.Google Scholar
Blandina, P., Goldfarb, J. & Green, J. P. (1988) Activation of a 5-HT2 receptor releases dopamine from rat striatal slices. European Journal of Pharmacology, 155, 349–350.Google Scholar
Bleeker, E. De & Verslegers, W. (1990) Ritanserin in the treatment of negative symptoms in chronic schizophrenic patients. Abstracts of the 17th Congress of CINP, Kyoto, Japan, Vol. II, p. 221.Google Scholar
Bunney, B. S. (1988) Effects of acute and chronic neuroleptic treatment on the activity of midbrain dopamine neurons. Annals of the New York Academy of Science, 537, 77–85.Google Scholar
Bunney, B. S. & Grace, A. A. (1978) Acute and chronic haloperidol treatment: comparison of effects on nigral dopaminergic activity. Life Sciences, 23, 1715–1728.Google Scholar
Burki, H. R., Ruch, W. & Asper, H. (1975) Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacology, 41, 27–33.Google Scholar
Caldwell, A. E. (1978) History of psychopharmacology. In Principles of Psychopharmacology (2nd edn) (eds Clark, W. G. & del Guidice, J.), pp. 9–40. New York: Academic Press.Google Scholar
Carlsson, A. (1988) The current status of dopamine hypothesis of schizophrenia. Neuropsychopharmacology, 1, 179–186.Google Scholar
Carlsson, A. & Carlsson, M. (1990) Possible neurotransmitter imbalances in schizophrenia. In Clinical Neuropharmacology: Proceedings from the 17th CINP Congress (eds Yamachita, I., Toru, M. & Coppen, A. J.), pp. 350–351. New York: Raven Press.Google Scholar
Caron, M., Sibley, D., Schwartz, J. C., et al (1991) Symposium. Molecular biology of the dopamine system: heterogeneity of the dopamine receptors. Abstract from 21st Annual Meeting of Society for Neuroscience, New Orleans, Louisiana, 1991.Google Scholar
Carpenter, W. T. Jr & Heinrich, D. W. (1981) Treatment-relevant subtypes of schizophrenia. Journal of Nervous and Mental Disease, 169, 113–119.Google Scholar
Carpenter, W. T. Jr & Heinrich, D. W. & Wagman, A. M. I. (1988) Deficit and non-deficit forms of schizophrenia: the concept. American Journal of Psychiatry, 145, 578–583.Google Scholar
Carpenter, W. T. Jr, Buchanan, R. W., Kirkpatrick, B., et al (1991) Negative symptoms: a critique of current approaches. In Negative versus Positive Schizophrenia (eds Marneros, A., Andreasen, N. C. & Tsuang, M. T.), pp. 126–133. Berlin: Springer-Verlag.Google Scholar
Casey, D. E. (1989a) Clozapine: neuroleptic induced EPS and tardive dyskinesia. Psychopharmacology, 99, 47–53.Google Scholar
Casey, D. E. (1989b) Serotonergic aspects of acute extrapyramidal syndromes in nonhuman primates. Psychopharmacology Bulletin, 25, 457–459.Google Scholar
Casey, D. E. (1991a) Serotonin and dopamine relationships in nonhuman primate extrapyramidal syndromes. Journal of European College of Neuropsychopharmacology, S15, 351–353.Google Scholar
Casey, D. E. (1991b) SCH 23390 and psychosis. Lancet, 338, 185.Google Scholar
Casey, D. E. (1992) Dopamine D1 (SCN-23390) and D2 (haloperidol) antagonists in drug-naive monkeys. Psychopharmacology, 107, 18–22.Google Scholar
Casey, D. E. & Raclopride Study Group (1991) A multicenter double-blind comparative trial of raclopride versus haloperidol in schizophrenia. Journal of European College of Neuropsychology, 46, 428–429.Google Scholar
Chiodo, L. A. & Bunney, B. S. (1983) Possible mechanisms by which repeated clozapine administration on the activity of A9 and A10 midbrain dopaminergic neurons. Journal of Neuroscience, 5, 2539–2544.Google Scholar
Chiodo, L. A. & Bunney, B. S. (1985) Possible mechanisms by which repeated clozapine administration differentially affects the activity of two subpopulations of midbrain dopamine neurons. Journal of Neuroscience, 5, 2539–2544.Google Scholar
Chouinard, G. & Annable, L. (1984) An early phase II clinical trial of BW 234U in the treatment of acute schizophrenia in newly admitted patients. Psychopharmacology, 84, 282–284.Google Scholar
Clark, D., Hjorth, S. & Carlsson, A. (1985a) Dopamine-receptor agonists: mechanisms underlying autoreceptor selectivity. I. Review of the evidence. Journal of Neural Transmission, 62, 1–52.Google Scholar
Clark, D., Hjorth, S. & Carlsson, A. (1985b) Dopamine-receptor agonists: mechanisms underlying autoreceptor selectivity. II. Theoretical considerations. Journal of Neural Transmission, 62, 171–207.Google Scholar
Coffin, V. L., Latranyi, M. B. & Chipkin, R. E. (1989) Acute extrapyramidal syndrome in Cebus monkeys: development mediated by dopamine D2 but not D1 receptors. Journal of Pharmacology and Experimental Therapeutics, 249, 769–777.Google Scholar
Cohen, B. M. & Lipinski, J. F. (1986) In vivo potencies of antipsychotic drugs in blocking α1 noradrenergic and dopamine D2 receptors: implications for drug mechanisms of action. Life Sciences, 39, 2571–2580.Google Scholar
Cohen, B. M. Keck, P. E., Stahir, A., et al (1991) Prevalence and severity of akathisia in patients on clozapine. Biological Psychiatry, 29, 1215–1219.Google Scholar
Cole, J. O., Goldberg, S. C. & Klerman, G. L. (1966) Phenothiazine treatment in acute schizophrenia. Archives of General Psychiatry, 10, 246–261.Google Scholar
Costall, B., Naylor, R. J. & Tyers, M. B. (1988) Recent advances in the neuropharmacology of 5-HT3 agonists and antagonists. Reviews in the Neurosciences, 2, 41–65.Google Scholar
Coward, D. M., Imperato, A., Urwyler, S., et al (1989) Biochemical and behavioral properties of clozapine. Psychopharmacology, 99, S6–S12.Google Scholar
Coward, D. M., Dixon, A. K., Urwyler, S., et al (1990) Partial dopamine-agonistic and atypical neuroleptic properties of the aminoergolines SDZ 208–911 and SDZ 208–912. Journal of Pharmacology and Experimental Therapeutics, 252, 279–285.Google Scholar
Creese, I., Burt, D. R. & Snyder, S. H. (1976) Dopamine receptor binder predicts clinical and pharmacological potencies of antischizophrenic drugs. Science, 192, 481–483.Google Scholar
Davis, J. M., Schaffer, C. B., Killian, G. A., et al (1980) Important issues in the drug treatment of schizophrenia. Schizophrenia Bulletin, 6, 70–87.Google Scholar
Delay, J., Deniker, P. & Hart, J. (1952) Traitement des états d'excitation et d'agitation par une méthode médicamenteuse dérivée de l'hibernothérapie. Annates Médico-psychologiques, 110, 267–273 Google Scholar
Delini-Stula, A. (1986) Neuroanatomical, neuropharmacological and neurobiochemical target systems for antipsychotic activity of neuroleptics. Pharmacopsychiatry, 19, 134–139.Google Scholar
Deutch, A. Y., Moghaddam, B., Innis, R. B., et al (1991) Mechanisms of action of atypical antipsychotic drugs: implications for novel therapeutic strategies for schizophrenia. Schizophrenia Research, 4, 121–156.Google Scholar
Ereshevsky, L., Watanabe, M. D. & Tran-Johnson, T. K. (1989) Clozapine: an atypical antipsychotic agent. Clinical Pharmacy, 8, 691–709.Google Scholar
Farde, L., Weisel, F. A., Janssen, P., et al (1988a) An open label trial of raclopride in acute schizophrenia: confirmation of D2-dopamine receptor occupancy by PET. Psychopharmacology, 94, 1–7.Google Scholar
Farde, L., Weisel, F. A., Halldin, C., et al (1988b) Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Archives of General Psychiatry, 45, 71.Google Scholar
Farde, L., Weisel, F. A., A., F., Nordstrom, A. L., et al (1989) D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology, 99, S28–S31.CrossRefGoogle ScholarPubMed
Fitton, A. & Heel, R. C. (1990) Clozapine – a review of its pharmacological properties and therapeutic use in schizophrenia. Drugs, 40, 722–747.Google Scholar
Fleischhacker, W. W., Miller, C. H. & Ehrmann, H. (1990) Ritanserin in the treatment of neuroleptic-induced akathisia (abstract). Schizophrenia Research, 3, 47.Google Scholar
Friedman, J. H. & Lannon, M. C. (1989) Clozapine in the treatment of pychosis in Parkinson's disease. Neurology, 39, 1219–1221.Google Scholar
Gelders, Y. G. (1989) Thymosthenic agents, a novel approach in the treatment of schizophrenia. British Journal of Psychiatry, 155 (suppl. 5), 33–36.Google Scholar
Gerlach, J. (1991) New antipsychotics: classification, efficacy, and adverse effects. Schizophrenia Bulletin, 17, 289–309.Google Scholar
Gerlach, J. & Casey, D. E. (1990) Remoxipride, a new selective D2 antagonist, and haloperidol in cebus monkeys. Progress in Neuro-psychopharmacology and Biological Psychiatry, 14, 103–112.Google Scholar
Gessa, G. L., Canu, A., Del Zompo, M., et al (1991) SCH 23390 and psychosis (letter). Lancet, 338, 185–186.Google Scholar
Gudelsky, G. A., Koenig, J. I., Simonovic, M., et al (1987) Differential effects of haloperidol, clozapine, and fluperlapine on tuberoinfundibular dopamine neurons and prolactin secretion in the rat. Journal of Neural Transmission, 68, 227–240.Google Scholar
Herve, D., Simon, H., Blanc, G., et al (1981) Opposite changes in dopamine utilization in the nucleus accumbens and the frontal cortex after electrolytic lesion of the median raphe in the rat. Brain Research, 216, 422–428.Google Scholar
Hippius, H. (1989) The history of clozapine. Psychopharmacology, 99, S3–S5.Google Scholar
Hornykiewicz, O. (1982) Brain catecholamines in schizophrenia –a good case for noradrenaline. Nature, 299, 484–486.Google Scholar
Jain, A. K., Kelwala, S., Moore, N., et al (1987) A controlled clinical trial of tiosperone in schizophrenia. International Clinical Psychopharmacology, 2, 129–135.Google Scholar
Javitt, D. C. & Zukin, S. R. (1990) The role of excitatory amino acids in neuropsychiatric illness. Journal of Neuropsychiatry and Clinical Neurosciences, 2, 44–52.Google Scholar
Kammen, P. P. van, Peters, J., Yso, J., et al (1990) Norepinephrine in acute exacerbations of chronic schizophrenia: negative symptoms revisited. Archives of General Psychiatry, 47, 161–170.Google Scholar
Kane, J. M. (1989) The current status of neuroleptic therapy. Journal of Clinical Psychiatry, 50, 322–328.Google Scholar
Kane, J. M., Cooper, T. B., Sachar, E. J., et al (1981) Clozapine: plasma levels and prolactin response. Psychopharmacology, 73, 184–187.Google Scholar
Kane, J., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment–resistant schizophrenic: a double-blind comparison versus chlorpromazine/benztropine. Archives of General Psychiatry, 45, 789–796.Google Scholar
Kane, J. M., Woerner, M., Safferman, A., et al (1991) Does clozapine cause tardive dyskinesia? Journal of Clinical Psychiatry (in press).Google Scholar
Köhler, C., Ogren, S. O. & Fuxe, K. (1984) Studies on the mechanism of action of substituted benzamide drugs. Acta Physiologica Scandinavica, 69, 125–137.Google Scholar
Lane, R. F., Blaha, C. D. & Rivet, J. M. (1988) Selective inhibition of mesolimbic dopamine release following chronic administration of clozapine: involvement of α1-noradrenergic receptor demonstrated by in vivo voltammetry. Brain Research, 460, 398–401.Google Scholar
Largent, B. L., Wikstrom, H., Snowman, A. M., et al (1988) Novel antipsychotic drugs share high affinity for sigma receptors. European Journal of Pharmacology, 155, 345–347.Google Scholar
Lewander, T., Westerbergh, S. E. & Morrison, D. (1990) Clinical profile of remoxipride – a combined analysis of a comparative double-blind multicentre trial programme. Acta Psychiatrica Scandinavica, 82 (suppl. 358), 92–98.Google Scholar
Leysen, J. E., Gommeren, W., Eens, A., et al (1988) The biochemical profile of risperidone, a new antipsychotic. Journal of Pharmacology and Experimental Therapeutics, 241, 661–670.Google Scholar
Lieberman, J., Kane, J. & Johns, C. (1989a) Clozapine: guidelines for clinical management. Journal of Clinical Psychiatry, 50, 329–338.Google Scholar
Lieberman, J., Johns, C., Cooper, T., et al (19896) Clozapine pharmacology and tardive dyskinesia. Psychopharmacology, 99, 54–59.Google Scholar
Lieberman, J., Saltz, B. L., Johns, C. A., et al (1991a) The effects of clozapine on tardive dyskinesia. British Journal of Psychiatry, 158, 503–510.Google Scholar
Lieberman, J., Johns, C., Pollack, S., et al (1991b) Biochemical effects of clozapine in cerebrospinal fluid of patients with schizophrenia. In Schizophrenia Research – Advances in Neuropsychiatry and Psychopharmacology (eds Schulz, S. C. & Tamminga, C. A.), pp. 341–349. New York: Raven Press.Google Scholar
Lindstrom, L. H. (1988) The effect of long-term treatment with clozapine in schizophrenia: a retrospective study in 96 patients treated with clozapine for up to 13 years. Acta Psychiatrica Scandinavica, 77, 524–529.Google Scholar
Ljundberg, T. & Ungerstedt, U. (1978) Classification of neuroleptic drugs according to their ability to inhibit apomorphine-induced locomotion and gnawing: evidence for two different mechanisms of action. Psychopharmacology, 56, 239–247.Google Scholar
Lowe, J. A. III, Seeger, T. F. & Vinick, F. J. (1988) Atypical antipsychotics: recent findings and new perspectives. Medical Research Reviews, 8, 475–497.Google Scholar
Mansour, A., Meador-Woodruff, I., Burke, S., et al (1991) Differential distribution of D2 and D4 dopamine receptor mRNAs in the rat brain: an in situ hybridization. Abstract from 21st Annual Meeting of Society for Neuroscience, New Orleans, Louisiana, 1991.Google Scholar
McKenna, D. J., Nazarali, A. J., Hoffman, A. J., et al (1989) Common receptors for hallucinogens in rat brain: a comparative autoradiographic study using (125I) LSD and (125I)DOL, a new psychotomimetic radioligand. Brain Research, 476, 45–56.Google Scholar
Meco, G., Bedini, J., Bonifati, V., et al (1989) Risperidone in the treatment of chronic schizophrenia with tardive dyskinesia: a single-blind crossover study versus placebo. Current Therapeutic Research, 46, 876–883 Google Scholar
Meltzer, H. Y. (1980) Relevance of dopamine autoreceptors for psychiatry: clinical and preclinical studies. Schizophrenia Bulletin, 6, 456–475.Google Scholar
Meltzer, H. Y. (1989) Clinical studies on the mechanism of action of clozapine: the dopamine–serotonin hypothesis of schizophrenia. Psychopharmacology, 99, 18–27.Google Scholar
Meltzer, H. Y. (1991) The mechanism of action of novel antipsychotic drugs. Schizophrenia Bulletin, 17, 263–287.Google Scholar
Meltzer, H. Y., Goode, D. J., Schyve, P. M., et al (1979) Effect of clozapine on human serum prolactin levels. American Journal of Psychiatry, 136, 1550–55.Google Scholar
Meltzer, H. Y., Bastani, B., Young Kwon, K., et al (1989a) A prospective study of clozapine in treatment-resistant schizophrenic patients. Psychopharmacology, 99, 68–72.Google Scholar
Meltzer, H. Y., Bastani, B., Ramirez, L. F., et al (1989b) Clozapine: new research on efficacy and mechanism of action. European Archives of Psychiatry and Neurological Science, 238, 332–339.Google Scholar
Meltzer, H. Y., Matsubara, S. & Lee, J.-C. (1989c) Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. Journal of Pharmacology and Experimental Therapeutics, 251, 238–246.Google Scholar
Mesotten, F., Suy, E., Pietquin, M., et al (1989) Therapeutic effect and safety of increasing doses of risperidone (R64766) in psychotic patients. Psychopharmacology, 99, 445–440.Google Scholar
Naber, D., Macher, J.-P., Gerlach, J., et al (1990) SDZ HDC 912 – a novel atypical antipsychotic agent: a four-week multi-center open therapeutic trial in schizophrenia. Abstracts of 17th Congress of CINP, Kyoto, Japan, Vol. II, p. 252.Google Scholar
Nemeroff, C. B., Kilts, C. D., Levant, B., et al (1991) Effects of the isomers of N-n-propylnorapomorphine and haloperidol on regional concentrations of neurotensin in rat brain. Neuro-psychopharmacology, 4, 27–33.Google Scholar
Olbrich, R. & Schanz, H. (1988) The effect of the partial dopamine agonist terguride on negative symptoms in schizophrenics. Pharmacopsychiatry, 21, 389–390.Google Scholar
Olney, J. W. (1989) Excitatory amino acids and neuropsychiatric disorders. Biological Psychiatry, 26, 505–525.Google Scholar
Owen, R. R., Beake, B. J., Marby, D., et al (1989) Response to clozapine in chronic psychotic patients. Psychopharmacology Bulletin, 25, 253–256.Google Scholar
Richelson, E. & Nelson, A. (1984) Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. European Journal of Pharmacology, 103, 197–204.Google Scholar
Roose, R. B., Theut, S. K., Banay-Schwartz, M., et al (1989) Glycine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: an open-label, pilot study. Clinical Neuropharmacology, 12, 416–424.Google Scholar
Rupniak, N. M. J., Hall, M. D., Mann, S., et al (1985) Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D-2 receptor function in the rat. Biochemical Pharmacology, 34, 2755–2763.Google Scholar
Safferman, A., Lieberman, J. A., Kane, J. M., et al (1991) Update on the clinical efficacy and side effects of clozapine. Schizophrenia Bulletin, 17, 247–261.Google Scholar
Schmutz, J. & Eichenberger, E. (1982) Clozapine. Chronicles Drug Discovery, 1, 39–59.Google Scholar
Seeman, P. (1987) Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse, 1, 133–152.Google Scholar
Seeman, P. (1990) Atypical neuroleptics: role of multiple receptors, endogenous dopamine, and receptor linkage. Acta Psychiatrica Scandinavica, 82 (suppl. 358), 14–20.Google Scholar
Seeman, P., Lee, T., Chau-Wong, M., et al (1976) Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature, 261, 717–719.Google Scholar
Seeman, P., & Ulpian, C. (1983) Neuroleptics have identical potencies in human brain limbic and putamen regions. European Journal of Pharmacology, 94, 145–148.Google Scholar
Snyder, S. H. & Largent, B. L. (1989) Receptor mechanisms in antipsychotic drug action: focus on sigma receptors. Journal of Neuropsychiatry, 1, 7–15.Google Scholar
Tamminga, C. A., Schaffer, M. H., Smith, R. C., et al (1978) Schizophrenic symptoms improve with apomorphine. Science, 200, 567–568.Google Scholar
Tamminga, C. A., Gotts, M. D., Thaker, G. K., et al (1986) Dopamine agonist treatment of schizophrenia with N-propylnorapomorphine. Archives of General Psychiatry, 43, 398–402.Google Scholar
Tamminga, C. A., Cascella, N. G., Lahti, R. A., et al (1992) Pharmacologic properties of (-) – 3PPP (preclamol) in man. Journal of Neural Transmission, 88, 165–175.Google Scholar
Tol, H. H. Van, Bunzow, J. R., Guan, H. C., et al (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature, 350, 610–614.Google Scholar
Waddington, J. L. (1988) Therapeutic potential of selective D-1 dopamine receptor agonists and antagonists in psychiatry and neurology. General Pharmacology, 19, 55–60.Google Scholar
Wadenberg, M. L. & Ahlenius, S. (1991) Antipsychotic-like profile of combined treatment with raclopride and 8-OH-DPAT in the rat: enhancement of antipsychotic-like effects without catalepsy. Journal of Neural Transmission – General Section, 83, 43–53.Google Scholar
Waldmeier, P. C. & Maitre, L. (1976) On the relevance of preferential increase of mesolimbic vs. striatal dopamine turnover for the prediction of antipsychotic activity of psychotropic drugs. Journal of Neurochemistry, 27, 589–597.Google Scholar
Waldmeier, P. C. & Delini-Stula, A. A. (1979) Serotonin–dopamine interactions in the nigrostriatal system. European Journal of Pharmacology, 55, 363–373.CrossRefGoogle ScholarPubMed
Walters, J. R. & Roth, R. H. (1976) Dopaminergic neurons: an in vivo system of measuring drug interactions with presynaptic receptors. Naunyn–Schmeideberg's Archives of Pharmacology, 296, 5–14.Google Scholar
White, F. J. & Wang, R. Y. (1983) Differential effects of typical and atypical antipsychotic drugs on A9 and A10 dopamine neurons. Science, 221, 1054–1057.Google Scholar
Wiedemann, K. & Benkert, O. (1990) B-HT920 – a novel dopamine autoreceptor agonist in the treatment of patients with schizophrenia. Pharmacopsychiatry, 23, 50–55.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.