No abstract

Raclopride, a highly selective D2-dopamine receptor antagonist, was administered in doses up to 4 mg b.i.d. to ten schizophrenic patients in an open label non-comparative study lasting 4 weeks. Safety, tolerability, potential antipsychotic effect, prolactin response and drug effect on plasma homovanillic acid were evaluated. Central D2-dopamine receptor occupancy was determined by positron emission tomography (PET). No major deviations were found in biochemical and physiological safety parameters. Raclopride was well tolerated. The mean BPRS score was reduced by 55% at endpoint. In the global evaluation seven patients were "very much" or "much" improved. Extrapyramidal side effects were recorded in four patients and disappeared after dose reduction or single doses of biperiden. An increase in plasma prolactin of short duration was observed in both sexes. A significant decrease of plasma HVA was obtained after 4 weeks of treatment. In two of the patients the central D2-dopamine receptors occupancy was measured using PET. The receptor occupancy was 68 and 72% which is the same as that found in patients treated with conventional neuroleptics.

No abstract

Following a 4-7 day drug-free washout period, eight male inpatients took an extended-release (ER) formulation of raclopride. After the initial 8 mg dose on day 1 of the study, repeated plasma samples were collected over the ensuing 36 h. Subsequently, patients received raclopride 8 mg b.i.d. through day 7, 12 mg b.i.d. through day 14, and, if tolerated, 16 mg b.i.d. through day 21. On days 7, 14, and 21, repeated plasma samples were drawn over the 12 h following the morning dose. Relative to the previously studied immediate release form of raclopride, the ER formulation delayed and extended the absorption of raclopride, and produced lower maximum raclopride concentrations. Linear kinetics were preserved across the dose range studied. Two patients could not tolerate the highest raclopride dose because of extrapyramidal side effects.

Biochemical and clinical effects of amiflaminedetermined by the debrisoquine hydroxylation phenotype ? Nord Psykiatr Tidsskr 1987; 41:141-148. Oslo ISSN 002%1455.Nine inpatients with a major depressive disorder were treated with the novel selective MAO-A inhibitor amiflamine at a dose of 2.5 mg b.i.d. for 3 weeks in an open study. Two patients who improved during this time continued with the same dose for another 3 weeks. (During a later depressive episode one of these patients was shown to be a placebo responder.) Six patients who did not respond during the first period were then given 5 mg b.i.d. for 3 weeks. One of these patients improved on this increased dosage. The most frequent adverse symptoms were difficulty in sleeping and headache. There was a pronounced variation in the plasma and cerebrospinal fluid (CSF) levels of the parent drug and mono-and didemethylmetabolites. One patient with extremely high levels of the parent drug (slow demethylator of amiflamine) was a slow hydroxylator of debrisoquine. Two other patients were rapid metabolizers of both drugs. There was no consistent effect on the levels of the amine metabolites S H I M , HVA or HMPG in CSF during treatment with amiflambe. The most pronounced decrease in 5-HIAA and HVA in CSF was seen in the patient with the highest drug plasma levels. It is suggested that in future studies the dosage of amiflamine is individualized depending on the metabolizing capacity of the patients. The dosage may be predicted by a debrisoquine test. Amine metabolites, Cerebrospinal fluid, Drug metabolism, MAO-A inhibitor.