Effects of nitroxazepine on diastolic blood pressure in mild hypertensive patients--a short term clinical study.

In a double blind short term clinical study, nitroxazepine has been found to be superior over placebo in reducing the diastolic blood pressure in mild hypertensive patients. In short term open clinical trial design nitroxazepine (25 mg PO, HS) has been found to be superior and better tolerated than diazepam (5 mg PO, HS). In open clinical trial design, nitroxazepine (25 mg PO, HS) reduced the diastolic blood pressure to the target level (100 mm Hg and less) effectively controlling the uncontrolled hypertensive patients receiving maintenance dose of beta blockers. There was no such beneficial effect in patients receiving maintenance doses of other antihypertensive drugs (pilot study). Adverse drug reactions like disturbed sleep in one, uneasiness in 3, palpitation in one and dryness of mouth in one patient have been observed.

Savoxepine: invalidation of an "atypical" neuroleptic response pattern predicted by animal models in an open clinical trial with schizophrenic patients.

The new tetracyclic compound savoxepine exhibits potent antidopaminergic effects with preferential activity in the hippocampus as compared to striatum in rat brain. As a result of behavioural animal models and regional differences in dopamine receptor binding characteristics, it has been suggested to possess an "atypical" neuroleptic response pattern. In an open clinical trial, savoxepine was administered to 12 in-patients suffering from paranoid schizophrenia and schizophreniform disorder (DSM-III). Eight patients were treated with a stable dose of 0.5 mg per day throughout the study, while in the remaining patients higher doses up to 20 mg/day were administered. Mean total BPRS scores and subscores demonstrated a moderate improvement of mainly positive schizophrenic symptoms. In contrast to animal test results, savoxepine in a broad dose range produced typical untoward extrapyramidal symptoms in the majority of patients. Our results indicate that savoxepine may not possess the expected "atypical" neuroleptic response pattern, and that the predictive validity of the animal models in question used to separate antipsychotic effects from extrapyramidal reactions may be ill-founded.

Efficacy and tolerability of a new antipsychotic compound (savoxepine): results of a pilot-study.

Savoxepine is a new tetracyclic compound displaying potent neurolepticlike effects in pharmacological studies. Of particular interest is its preferential binding to dopamine-2 receptors in the hippocampus, which leads to the hypothesis that savoxepine may exert antipsychotic effects at doses not inducing extrapyramidal side-effects. In an open pilot-study 18 patients suffering from acute schizophrenic psychoses or paranoid syndromes were treated with savoxepine in an individually adapted dose range from 0.50 to 10 mg per day. A good antipsychotic efficacy could be demonstrated in 10 of 16 patients. Savoxepine was found to be generally well tolerated. Contrary to expectations, mild or moderate extrapyramidal side-effects, especially of the parkinsonian type, were registered. Future research has to test the suggested advantage of savoxepine in comparison with other neuroleptic drugs.

Amoxapine-induced neuroleptic malignant syndrome.

Amoxapine is a second-generation antidepressant possessing significant dopamine-blocking activity and extra-pyramidal side effects. The occurrence of neuroleptic malignant syndrome is described in a patient treated with amoxapine. The syndrome resolved rapidly following discontinuation of the drug. Older patients may be particularly at risk for this adverse reaction with amoxapine.

EGYT-2509 a novel neuroleptic agent without extrapyramidal and endocrine side effects.

The dibenzodioxazocine derivative EGYT-2509 was effective in neuropsychopharmacological tests characteristic for neuroleptics and antiparkinsonian drugs. It interacted with dopaminergic compounds similarly to chlorpromazine and haloperidol, but in certain tests it showed different activity. Similarly to chlorpromazine and haloperidol it inhibited the lethal effect of amphetamine in grouped mice. The apomorphine-induced stereotypy was potentiated by lower, and antagonized by higher doses of EGYT-2509. The compound did not show cataleptogenic activity and even antagonized the catalepsy evoked by bulbocapnine. The in vitro potency of EGYT-2509 to block dopamine-mediated inhibition of prolactin release was weaker by three orders of magnitude than that of haloperidol. In preliminary human studies it did not affect the plasma prolactin level. It is concluded that EGYT-2509 is a new potential antipsychotic agent with minimal risk of extrapyramidal and endocrine side effects.

Amoxapine-induced cognitive impairment in two patients.

Two patients are described in whom subtle cognitive impairments are associated with therapeutic doses of amoxapine. The implications of this observation for the management of depression, particularly in patients with coexisting dementing illnesses, are discussed.

Tardive myoclonus.

We describe a 46-year-old, schizophrenic woman with late-onset myoclonus after treatment with antipsychotic drugs. The myoclonic jerking of the neck with synchronous contractions of the face persisted after all the antipsychotic drugs had been discontinued. Tardive myoclonus has not been documented previously.