Abstract
RMI-81,582 (2-chioro-11-3-dimethylaminopropylidene morphanthridene), a potential antipsychotic agent, was administered to eight chronic and four acute male schizophrenics in an open label study. Ten of twelve patients improved, particularly those who were experiencing their first hospitalization, regardless of whether they met Research Diagnostic Criteria for acute or chronic schizophrenia. Significant improvement was noted on the Clinical Global Impressions and Brief Psychiatric Rating Scale. No extrapyramidal side effects were noted and other adverse reactions were few. Serum prolactin levels, a measure of antidopaminergic activity, were increased by low-moderate dosages of RMI-81,582 in seven of eleven patients. Four patients had no increase in serum prolactin with RMI-81,582. In six of the seven patients who developed increases in serum prolactin, prolactin levels returned to those characteristic of the placebo period as the dosage of RMI-81,582 was increased. With classical neuroleptics, serum prolactin levels increase as the dose increases up to approximately the equivalent of chlorpromazine 600 mg/day and then remain fairly constant. The pattern of serum prolactin response in both man and laboratory animals and the absence of extrapyramidal side effects suggest RMI-81,582 may have a clozapine-like action.
Similar content being viewed by others
References
Amsler, H. A., Teerenhovi, L., Barth, E., Hargula, K., Vuopio, P.: Agranulocytosis in patients treated with clozapine. A study of the Finnish epidemic. Acta Psychiatr. Scand. 56, 241–248 (1977)
Angrist, B., Rotrosen, J., Aronson, M., Gershon, S.: A morphanthridine derivative in schizophrenic patients — lack of extrapyramidal symptoms. Curr. Ther. Res. Clin. Exp. 20, 94–99 (1976)
Battegay, R., Cotar, B., Fleischhauer, J., Rauchfleisch, U.: Results and side effects of treatment with clozapine (LeponexGf). Compr. Psychiatry 18, 423–428 (1977)
Bjerkenstedt, L., Eneroth, P., Harnryd, C., Sedvall, G.: Effects of Melperone and thiothixene on prolactin levels in cerebrospinal fluid and plasma of psychotic women. Arch. Psychiatr. Nervenkr. 224, 281–293 (1977a)
Bjerkenstedt, L., Gullberg, B., Harnryd, C., Sedvall, G.: Monoamine metabolite levels in cerebrospinal fluid of psychotic women treated with Melperone or thiothixene. Arch. Psychiatr. Nervenkr. 224, 107–118 (1977b)
Bjerkenstedt, L., Harnryd, C., Grimm, V., Gullberg, B., Sedvall, G.: A double-blind comparison of Melperone and thiothixene in psychotic women using a new rating scale, the CPRS. Arch. Psychiatr. Nervenkr. 226, 157–172 (1978)
Bowers, M. B., Jr., Heninger, G. R., Meltzer, H. Y.: Plasma and CSF dopamine metabolites in psychiatric patient: Effects of probenecid and haloperidol. In: Catecholamines: Basic and clinical frontiers. Vol. II. E. Usdin, I. J. Kopin, J. Barchas, eds., pp. 1893–1895. New York: Pergamon Press 1979
Carlsson, A., Persson, T., Roos, B. E., Wålinder, J.: Potentiation of phenothiazines by α-methyltyrosine in treatment of chronic schizophrenia. Neural Transm. 33, 83–90 (1972).
Carlsson, A., Roos, B.-E., Wålinder, J., Skott, A.: Further studies on the mechanism of antipsychotic action: potentiation of α-methyltyrosine of thioridazine effects in chronic schizophrenics. J. Neural Transm. 34, 125–132 (1973)
Carlsson, A.: Does dopamine play a role in schizophrenia? Psychol. Med. 7, 585–597 (1977)
Clemens, J. A., Smalstig, E. B., Sawyer, B. D.: Anti-psychotic drugs stimulate prolactin release. Psychopharmacologia (Berl.) 40, 123–127 (1974)
Gianutsos, G., Moore, K. E.: Possible significance of clozapine-induced increase in brain dopamine. Res. Commun. Chem. Pathol. Pharmacol. 17, 29–39 (1977)
Honigfeld, G., Klett, J.: Nurses observation scale for in patient evaluation (NOSIE). Clin. Psychol. 21, 65–71 (1965)
Hwang, P., Guyda, H., Friesen, H.: A radioimmunoassay for human prolactin. Proc. Natl. Acad. Sci. USA 68, 1902–1906 (1971)
Hyttel, J.: Effect of neuroleptics on the disappearance rate of 14C labelled catecholamines formed from 14C tyrosine in mouse brain. Pharm. Pharmacol. 26, 29–39 (1977)
Lehmann, H. E., Ban, T. A., Deutsch, M.: An uncontrolled clinical study with EX 11-582A in the treatment of chronic schizophrenic patients. Psychopharmacol. Bull. 13, 7–9 (1977)
Meltzer, H. Y., Daniels, S., Fang, V. S.: Clozapine increases rat serum prolactin levels. Life Sci. 17, 339–342 (1975)
Meltzer, H. Y., Fang, V. S.: The effect of neuroleptics on serum prolactin levels in schizophrenic patients. Arch. Gen. Psychiatry 30, 279–286 (1976)
Meltzer, H. Y., Goode, D. J., Fang, V. S.: The effect of psychotropic drugs on endocrine function. I. Neuroleptics, precursors and agonists. In: Psychopharmacology: A generation of progress. A. Lipton, A. DiMascio, K. F. Killam, eds., pp. 509–529. New York: Raven Press 1978
Meltzer, H. Y., Goode, D. J. Schyve, P. M., Young, M. A., Fang, V. S.: Effect of clozapine on human serum prolactin levels. Arch. Gen. Psychiatry (in press, 1979)
Overall, J. E., Gorham, D. R.: The brief psychiatric rating scale (BPRS) Psychol. Rep. 10, 799–812 (1962)
Pearl, D., van der, Kamp, H., Olsen, A. L., Greenberg, P. O., Armitage, S. G.: The effects of reserpine on schizophrenic patients. Arch. Neurol. Psychiatry 76, 198–204 (1956)
Richardson-Merrill, Inc., Investigational Brochure, RMI-81,582, 1972
Seeman, P., Chau-Wong, M., Tedesco, J., Wong, K.: Brain receptors for antipsychotic drugs and dopamine: direct binding assays. Proc. Natl. Acad. Sci. USA 72, 4376–4380 (1975)
Simpson, G. M., Zoubok, B., Lee, J. H.: An early clinical and toxicty trial of EX 11-582A in chronic schizophrenia. Curr. Ther. Res. 19, 87–93 (1976)
Snyder, S. H., Banerjee, S. P., Yamamura, H. I., Greenberg, D.: Drugs, neurotransmitter, and schizophrenia. Science 184, 1243–1253 (1974)
Weissman, A., Koe, B. K.: Behavioral effects of 1-α-methyltyrosine, an inhibitor of tyrosine hydrozylase. Life Sci. 4, 1037–1048 (1965)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Young, M.A., Meltzer, H.Y. RMI-81,582, a novel antipsychotic drug. Psychopharmacology 67, 101–106 (1980). https://doi.org/10.1007/BF00427603
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00427603