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At least 19 recordsLinked to original sources
PubMed1978

Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

Animals↗
PubMed1979

Ultrastructure of rat lungs following exposure to aerosols of dibenzoxazepine (CR).

Three groups of 18 animals were exposed respectively to the following large doses of dibenz (b.f)-1:4 oxazepine (CR) aerosols, 78,200,140,900 and 161,300 mg/min/m3. Animals were killed at intervals from 15 min to 2 days, and the lungs examined macroscopically, by electron microscopy and conventional histology. There were no deaths during or after exposure. Macroscopically the lungs from all rats appeared normal. Microscopically there were a few areas of mild congestion, haemorrhage and emphysema, but there was little variation between the different groups. Electron micrographs revealed some morphological alteration of the epithelium and endothelium but only occasional changes in the interstitium. The alterations took the form of "ballooning" of the endothelium with isolated foci of swelling and thickening of the epithelium. Interstitial oedema was observed in one animal only which was exposed to the highest concentration. The effects appeared similar in all groups, and are thought to be transient. The results of this investigation suggest that even high doses of CR aerosols cause minimal damage to the lung, and the structural alterations which do occur are believed to be due to the stress to which the animals were subjected during the exposure period.

Aerosols↗
PubMed1977

Adenylate cyclase from various dopaminergic areas of the brain and the action of loxapine.

The present report is a comparative study of adenylate cyclase activity in various areas of the brain identified as dopaminergic. Low levels of dopamine were found to stimulate adenylate cyclase from the striatum, median eminence, olfactory tubercle, nucleus accumbens and amygdala. Apomorphine, known to mimic the pharmacological and physiological effects of dopamine, stimulated adenylate cyclase from these areas. Several different classes of drugs effective in the treatment of schizophrenia were potent inhibitors of the stimulation by dopamine of the enzyme from these various regions. The drugs studied included representatives of the phenothiazine, butyrophenone, dibenzodiazepine and dibenzoxazepine classes. The inhibition by the dibenzoxazepine, loxapine, which is structurally very similar to the dibenzodiazepine, clozapine, was competitive with respect to dopamine. The calculated inhibition constant (Ki) for loxapine of about 15 nM was similar to that observed for some of the more potent phenothiazines. The results, considered together with previously published data, support the possibility that the therapeutic effects as well as the extrapyramidal and endocrinological side effects, of these antipsychotic agents may be attributable to their ability to block the activation of adenylate cyclase in various select areas of the brain.

Adenylyl Cyclase Inhibitors↗
PubMed1979

Amoxapine versus amitriptyline in endogenous depression. A double-blind study.

A new antidepressant, amoxapine, which is a dibenzoxazepine deprivative, was compared with amitriptyline in a randomised double-blind trial. Forty-eight patients were included and 41 completed a 4-week treatment. Most of the patients were maintained on 150 mg daily. Assessments were made by the Hamilton Psychiatric Rating Scale for Depression (HAM-D), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), Clinical Global Impression (CGI) scale and Patient's Self-Evaluation. The total HAM-D score was considerably reduced in the majority of the patients. Amitriptyline was the most effective with regard to symptoms included in the factor Sleep Disturbances and-secondary maybe-towards some items included in the factor Somatization. For the remaining items,including the items of the factors Anxiety/Depression and Apathy, the last score was lower in the amoxapine group than in those treated with amitriptyline. Among the unipolar cases the amoxapine treated patients were more satisfied with regard to efficacy (P = 6.3%). The frequency of side effects such as tremor and dizziness was considerably lower in the amoxapine group. In total, the side effects lasted longer in the amitriptyline group. We conclude that amoxapine seems to be an effective antidepressant with a low frequency of side effects.

Adult↗
PubMed1978

Loxapine: a review of its pharmacological properties and therapeutic efficacy as an antipsychotic agent.

Loxapine is a dibenzoxazepine, tricyclic compound recommended for the treatment of acute and chronic schizophrenia. In its therapeutic effectiveness and profile and incidence of side-effects, loxapine closely resembles the traditional antipsychotic agents. Although loxapine has tended to be less effective than some standard antipsychotic drugs in a few short-term (3 to 4 weeks) studies, it has been superior to a placebo and about as effective as chlorpromazine, haloperidol, trifluoperazine or thiothixene when evaluated after 4 to 12 weeks. Like the phenothiazine (e.g. chlorpromazine) and butyrophenone (e.g. haloperidol) antipsychotic agents, loxapine causes a high incidence of extrapyramidal reactions. Sedation occurs frequently, especially during early stages of treatment. Other, less common side-effects such as anticholinergic effects (dry mouth, blurred vision, etc.), hypotension, tachycardia and precipitation of epileptic seizures, which occur with the older antipsychotic drugs, have also been reported with loxapine.

Animals↗
PubMed1978

The neuropharmacological actions of amoxapine.

Amoxapine possesses a broad spectrum of psychotropic actions, including antidepressant and neuroleptic effects in animals. Antidepressant activity is characterized by its ability to inhibit tetrabenazine-induced depression, antagonize reserpine-induced hypothermia and enhance yohimbine lethality. Neuroleptic activity is demonstrated by the ability of amoxapine to decrease locomotor activity, induce ptosis and catalepsy, inhibit apomorphine gnawing and amphetamine stereotyped behavior and by characteristic changes in monkey discriminated avoidance behavior. The fact that punished responding in squirrel monkeys was present was present after repeated administration may indicate an anti-anxiety action of this drug. Evidence is offered that the conversion of the tertiary terminal nitrogen to a secondary amine may alter the pharmacologica properties of dibenzoxazepines in a similar way to the for the phenothiazines.

Amoxapine↗
PubMed1976

Tardive dyskinesia.

The etiology, pharmacology, treatment and possible prevention of tardive dyskinesia (TD) are discussed. This neurological disorder, characterized by involuntary movements of the lips, jaws and tongue, can occur as a result of short-term antipsychotic drug therapy, but usually occurs after long-term treatment. Phenothiazines, the thioxanthines, butyrophenones, dibenzoxazepines and dihydroindolines also posess the potential for inducing TD. Methods of treatment of TD with dopamine-depleting agents, dopamine-blocking agents and cholinomimetics are discussed. Despite the apparent effectiveness of some drugs in the treatment of TD, it should be kept in mind that most of the studies demonstrating drug effectiveness involved a small number of patients.

Choline↗
PubMed1978

Major side effects of antipsychotic drugs.

Since the introduction of phenothiazines into clinical practice in 1952, over 250 million people have received these drugs for the treatment of psychotic states. In addition to the phenothiazines, five other classes of neuroleptic medications are now in use: butyrophenones, thioxanthenes, dihydroindolones, diphenylbutylpiperidines, and dibenzoxazepines. Besides their use in the treatment of psychosis, these drugs have been used in the treatment of anxiety, depression, nausea, alcoholic withdrawal, and pain, and are often administered in combination with other medications. Through the use of these drugs, many psychotic patients have been able to move back into the community, and the family physician is coming into contact with more patients on maintenance dosages of neuroleptics. He/she may wish to prescribe these drugs or may, in the treatment of a medical problem, need to prescribe other medication to an individual already receiving neuroleptics. It is important, therefore, for the family physician to be aware of the side effects of these drugs and of complications which can arise when neuroleptics are given in combination with other families of drugs.

Butyrophenones↗
PubMed1978

Relation of plasma prolactin to clinical response in schizophrenic patients.

It has been suggested that, if dopamine antagonism is a necessary condition for the antischizophrenic action of neuroleptics, the prolactin response, as an index of dopamine blockade, would correlate with clinical response. Morning prolactin and clinical symptomatology were measured in 15 schizophrenic patients before neuroleptic therapy, and after three and six weeks of high-dose butaperazine or loxapine treatment. Prolactin levels were transiently elevated during the unmedicated admission period, probably reflecting a normal stress response. Prolactin increased in all patients during neuroleptic therapy. There was, however, no correlation between magnitude of prolactin changes and clinical response, probably because the prolactin response achieved a maximum at relatively low doses of neuroleptics.

Adult↗
PubMed1975

Loxapine in newly admitted chronic schizophrenic patients.

The standard drug Stelazine (STEL), at a dose of 50 mg/day, exhibited therapeutic activity significantly different from placebo (PL) activity on several variables, most notably BPRS, attesting to the sensitivity of the experiment. On the other hand, the investigational drug, loxapine (LOX), in doses of 100 mg/day for four weeks, could be differentiated from PL as treatment in the described population on only one variable (NGI-Imp.) and one item of the BPRS. On several variables, positive trends were noted, but the differences from PL did not attain the critical values necessary for statistical significance at P smaller than 0.05. One might speculate that the relatively short duration of treatment in this study might account for the difference between these disappointing results and the more gratifying results of a previous loxapine study in chronic long-term institutionalized schizophrenics with the same oral dose.

Adult↗
PubMed1976

A double-blind comparison of loxapine succinate and trifluoperazine in newly admitted schizophrenic patients.

A study was conducted evaluating the efficacy of loxapine succinate in newly admitted schizophrenic patients through a four-week double-blind comparison with trifluoperazine. Twenty-four patients received between 40 and 80 mg loxapine succinate daily and 19 patients received between 20 and 50 mg trifluoperazine daily. The two groups showed comparable significant improvement on the BPRS and CGI. The discharge and termination rates of the two groups were not significantly different and the incidence and severity of side effects, most frequently extrapyramidal signs, were similar in both groups. Loxapine succinate was judged to be an effective treatment for newly admitted schizophrenic patients.

Adolescent↗
PubMed1975

GLC determination of 7-chloro-5,11-dihydrodibenz[b,e][1,4]-oxazepine-5-carboxamide in serum or plasma.

This report describes the isolation, derivative formation, GLC, and quantitation of unmetabolized 7-chloro-5,11-dihydrodibenz[b,e][1,4]oxazepine-5-carboxamide (I) in blood serum or plasma. Carbamazepine is used as the internal standard to compensate for losses of I during extraction and handling. Essentially complete recovery (100 +/- 6%) was demonstrated over a concentration range of 1-30 mug of I/ml of serum.

Chromatography, Gas↗
PubMed1976

Physical characterization and activity in vivo of polymorphic forms of 7-chloro-5, 11-dihydrodibenz[b, e][1, 4]oxazepine-5-carboxamide, a potential tricyclic antidepressant.

The biological availability in dogs and humans of 7-chloro-5, 11-dihydrodibenz[b,e][1,4]oxazepine-5-carboxamide, a potential antidepressant drug, was increased when the compound was administered in capsule formulations as micronized drug coated with 1% sodium lauryl sulfate or as a lyophilate with poloxamer 407. This increase with these two formulations had been predicted by dissolution tests in vitro. The lyophilized combination with poloxamer 407 was more soluble in 0.1 N HCl than was the untreated compound. Characterization of the lyophilate by differential thermal analysis, X-ray diffraction, and IR spectroscopy indicated that the increase in solubility was attributable to the formation of a polymorphic from. a polymorph of the compound designated form 8, was prepared. The solubility and dissolution characteristics of the two polymorphic forms, A and B, as well as of the lyophilized combination with poloxamer 407, were determined.

Adult↗
PubMed1979

GLC analysis of loxapine, amoxapine, and their metabolites in serum and urine.

A GLC analysis is presented for loxapine, amoxapine, and their major metabolites in serum and urine. Electron-capture detection is employed for serum analysis, and flame ionization is used for urine analysis. The procedure includes trifluoroacetylation of secondary amine functions, followed by trimethylsilylation of phenolic groups after ethyl acetate extraction of the sample. Urine requires prior enzymatic hydrolysis of conjugates. Data indicating the utility of the procedure in hospitalized patients and normal volunteers are presented.

Amoxapine↗