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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.

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.

Two patients are described who experienced seizures while on therapeutic doses of amoxapine. It is suggested that the structural similarities of amoxapine to the neuroleptics may account for side effects similar to the neuroleptic compounds, including seizures. Caution is encouraged in prescribing amoxapine to patients with a history of seizure disorder.

A case report of amoxapine-induced tardive dyskinesia following discontinuation of amoxapine therapy is reported. During 68 weeks of therapy, the patient received a maximum of amoxapine 400 mg/d. Six months after amoxapine discontinuation, the patient continued to have symptoms of tardive dyskinesia. These symptoms correlate with the dopamine receptor-blocking property of amoxapine and its metabolites. We propose that amoxapine therapy be monitored for the long-term as well as the short-term adverse effects of dopamine receptor-blockade.

A depressed woman who was treated with amoxapine developed akinesia, which was mistaken for depression. This extrapyramidal syndrome has not previously been linked with this widely used antidepressant, and clinicians should be aware of the association.

The authors describe a case of tardive dyskinesia and parkinsonism associated with amoxapine. Patients who develop acute parkinsonism while taking amoxapine may be at higher risk for tardive dyskinesia. The authors recommend that amoxapine be prescribed as carefully as other neuroleptics.

The antidepressant amoxapine is structurally related to the neuroleptic loxapine and can cause side effects related to hypothesized dopamine receptor blockade. This case of withdrawal dyskinesia after amoxapine discontinuation further demonstrates its potential for causing side effects associated with neuroleptics.

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.

Based on qualitative and quantitative EEG findings, the psychotropic properties of GB-94, GC-46, and GC-94 were predicted. According to the EEG model, GB-94 was predicted to be similar to amitriptyline and GC-46 t( imipramine. GC-94 was found to be much less effective on the CNS than GB-94 and GC-46 and was predicted to have "stimulatory" clinical effects similar to desipramine. The clinical trials demonstrated that GB-94 is indeed an antidepressive psychotropic compound similar to amitriptyline. GB-94 in lower dosages was also found to be effective in anxiety syndromes. In some schizophrenics GB-94 showed some therapeutic effects, while in others it obviously exacerbrated the psychotic symptomatology. GC-94 was not found to be significantly effective in a heterogenous psychiatric population. Only slight improvement in some schizophrenic patients was observed However, a noticeable worsening in the symptomatology of manic and hypomanic patients was seen. The study demonstarted that GC-94 indeed has a central stimulatory effect, but no minor or major tranquilizer properties or sedative antidepressive qualities were observed. GC-46 was tried in only three subjects. Based on this pilot trial, no conclusion can be made about the psychotropic properties of this compound. Our quantitative pharmaco-EEG and clinical trials clearly demonstrated the significant value of quantitative EEG in early screening of psychoactive drugs in order to predict their clinical values and effective dosage ranges.

1,3,4,14b-Tetrahydro-2,7-dimethyl-2H-dibenzo(b,f)pyrazino-(1,2-d)-(1,4)-oxazepine hydrogen maleate (Org GC 94) is an oral "antamine" preparation with anti-serotoninergic and anti-histaminic effects. Its lack of unpleasant side-effects permits protracted use for the preventive treatment of serotonin-migraine. Its chemical structure--tetracyclic ring, C-beta, C-alpha, amine in a secondary position--allows block of the receptors for serotonin and histamine. Preventive treatment with 3 x 5 mg/day of Org GC 94 for a period of 3 months can almost completely eliminate migraine attacks. 21 out of 30 patients (70%) profited from such a treatment, showing a drop from 5--30 attacks to 0--1 attack per month and normalization of high urinary serotonin, 5-HIAA or histamine levels. However, 30 patients receiving 3 x 0.5 mg or placebo daily reacted only rarely. The typical side-effects of anti-serotonin drugs, especially sedation or dizziness and hyperorexia were hardly observed. Randomization of the serotonin-migraine cases and double-blind methodology were applied throughout the trial.

A case of nonketotic hyperglycemic coma associated with the recent introduction of loxapine is presented. Drug discontinuation led to a return of normal fasting blood glucose. Later challenge with amoxapine was also associated with acute hyperglycemia. Their common metabolite, 7-OH amoxapine, is implicated.

Two patients with depression were treated with amoxapine for 3 to 5 years and subsequently developed persistent tardive dyskinesia. The author stresses caution in regard to the long term use of amoxapine.

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.

The authors describe a case of oral-facial dyskinesia that occurred after discontinuation of amoxapine, and antidepressant which may also have neuroleptic effects. Occurrence of withdrawal dyskinesia indicates that the neuroleptic effects of amoxapine may be clinically significant.

The phagocytosis of Staphylococcus epidermis by rabbit alveolar macrophages was measured in the absence or presence of a series of sensory irritants. The phagocytic index was determined in the presence of the sensory irritant dibenzoxazepine and 10 of its derivatives. All of the compounds tested inhibited phagocytosis to some extent. Dibenzoxazepine was the most potent inhibitor and the 1-chloro and 2-chloro derivatives were the least potent. With all the compounds tested, the inhibition of phagocytosis was dose dependent. The degree of inhibition of phagocytosis was not correlated with either the nature or the position of the substituent groups on the dibenzoxazepine molecule. There was no discernible relationship between the inhibition of phagocytosis and the irritancy of the compounds tested.

Methodological questions of clinical observation and classification of drug-induced extrapyramidal symptomatology are discussed. In our experimental approach we examined two groups of 20 acute schizophrenic patients each. The patients were treated for 4 weeks under double-blind conditions with the butyrophenone derivative Haloperidol and with the benzoxazepine derivative Loxapin respectively. The extrapyramidal disturbances appearing under these medications were studied. The patients were examined by means of the EPS-scale by Simpson and Angus weekly, before, during and after this treatment as well as under a subsequent therapy with a longacting neuroleptic. Extrapyramidal disturbances appearing between these fixed rating times were noted in a check list. According to a classification propased by Chien and Di-Mascio the symptomatology of extrapyramidal disturbances under neuroleptic therapy can be divided into "permanent neuroleptic manifestations" on the one hand and "paroxysmal neurodysleptic manifestations" on the other. While Haloperidol caused more distinct symptoms of permanent neuroleptic manifestations, acute neurodysleptic reactions appeared more frequently under Loxapin therapy.

Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening complication of neuroleptic therapy. Its occurrence is not familiar to most emergency physicians. Early recognition and appropriate management of NMS may prevent significant morbidity and mortality.

A case is reported of neuroleptic-induced catatonia that developed after treatment with loxapine succinate, a drug not previously reported to cause catatonia. The syndrome, characterized by marked parkinsonism, episodes of posturing, social withdrawal, and urinary incontinence, persisted during haloperidol treatment and remitted when the drug was discontinued. This syndrome appears to represent severe neuroleptic-induced parkinsonism.