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At least 19 recordsLinked to original sources
PubMed1977

Synthesis of some dibenzazepines of possible therapeutic interest.

Among the hypotensive drugs are the N-alkyldibenz[c,e]-azepines. A representative of this class is 6-allyl-6,7-dihydro-5H-dibenz[c,e]azepine (azapetine). The present investigation involved the preparation of a new series of N-[6,7-dihydro-5H-dibenz[c,e]azepin-6-yl] acid amides namely; acetamide, benzamide, phehyl acetamide, salicylamide and p-hydroxybenzamide derivatives. Another new series of N-[6,7-dihydro-5H-dibenz[c,e]azepin-6-yl]-N-alkyl (or aryl) thioureas was prepared namely ethyl, isopropyl, butyl, cyclohexyl, benzyl, phenyl and o-tolyl thiourea derivatives. IR spectra of the two series of compounds were investigated.

Antihypertensive Agents↗
PubMed1975

Enhancement of the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea by various psychotropic drugs in combination with caffeine.

Certain psychotropic drugs when combined with caffeine significantly enhanced the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea in murine leukemia L1210. Enhancement required that all three drugs be given together and optimal results were obtained when the psychotropic drug was given 6 hours before 1,3-bis(2-chloroethyl)-1-nitrosourea and caffeine. Thus, 1,3-bis(2-chloroethyl)-1-nitrosourea alone or with caffeine resulted in 5% cures. Addition of chlorpromazine increased the cure rate to 51% while prochlorperazine gave 30% cures. Chlordiazepoxide produced 39% cures while the dibenzazepine compounds studied were ineffective. For the phenothiazine, benzodiazepine and dibenzazepine compounds studied, tentative conclusions could be drawn on the relationship of chemical structure to enhancing activity. For phenothiazines, the substituent in the R2 position of the phenothiazine ring determined activity to a greater extent than did the substituent in the R1 position. For the benzodiazepine compounds, chlordiazepoxide was superior to diazepam. Although the mechanism of action of psychotropic drugs in this system is unknown, these preliminary results suggest the possibility of a change transfer reaction between the free radical form of the psychotropic drug and one or more intracellular constituents.

Animals↗
PubMed1979

Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients: a controlled, double-blind comparison.

Clozapine is a unique compound belonging to a relatively new group of antipsychotic agents, the dibenzazepines. To our knowledge, the present study represents the first double-blind, controlled comparison recorded in the United States. The data suggest that clozapine in the present population of newly admitted, acutely psychotic schizophrenic individuals, and in the doses employed, was more effective in overall improvement response, discharge rate, and ameliorating discrete symptoms across the different objective rating scales used than was chlorpromazine (Thorazine) hydrochloride. Placebo was ineffective. Unlike chlorpromazine, no extrapyramidal reactions occurred in those patients ingesting clozapine. Clozapine was also beneficial in reversing abnormal involuntary motor movements. It is an excellent anxiolytic and hypnotic agent. Sedation, hypotension, and hypersalivation are among the more common side effects observed.

Acute Disease↗
PubMed1977

Some effects of mianserine (ORG GB 94) on amine metabolism in the rat brain.

The effects of the tetracyclic antidepressant drug mainserine (code Nr. ORG GB 94) on biogenic amine metabolism in the rat brain are summarized. After either acute or chronic administration, mianserine increases the turnover of noradrenaline without appreciably affecting that of dopamine or serotonin. No evidence can be found that it affects amine reuptake in vivo. In its effect on amine turnover and reuptake, mianserine differs qualitatively from the dibenzazepine antidepressants. It is concluded that drugs need not be amine reuptake inhibitors before they are considered to be potential antidepressants.

Animals↗
PubMed1978

Structure-activity relationships for the anticholinoceptor action of tricyclic antidepressants.

1 The anticholinoceptor action of 15 tricyclic antidepressants and derivatives has been studied on the guinea-pig ileum. At the muscarinic receptors the compounds were found to exert antagonism which was reversible and apparently competitive up to dose-ratios of around 100 but non-competitive above this level. 2 Log affinity constants were derived from log dose-response curves at dose-ratios less than 100, where parallel curves were obtained. Amitriptyline, the most potent compound, had 214 X the potency of the weakest, hydroxyimipramine, but was itself 20 X weaker than atropine. 3 Structure-activity studies showed that dibenzocycloheptane derivatives were more potent than dibenzazepines and that S or O substitution for C-11 or other major changes in the central ring of the tricyclic nucleus greatly reduced activity. Side-chain N-methylation increased potency markedly. This and other findings indicate that both tricyclic nucleus and side-chain receptor attachments are largely non-polar in type.

Acetylcholine↗
PubMed1977

Tricyclic antidepressant toxicity.

Tricyclic antidepressants are dibenzazepine derivatives with adrenergic, anticholinergic, and direct cardio-depressant activity. Double-blind clinical studies show TCAD to be efficacious for two-thirds of depressed patients. Cardiac toxicity is significant, especially on diseased myocardium. Serious arrhythmias and intracardiac blocks have been reported on therapeutic doses. Tricyclic antidepressant overdose is a serious condition which is becoming progressively more common. The agents' principal toxicities are to the nervous system and the heart. The syndrome can be divided into three stages of varying severity. The vast majority of cases are in the mild Stage I. Some patients reach Stage II with major CNS effects and increasing intracardiac block. Stage III, which encompassed less than 5% of poisonings, is a potentially fatal situation with respiratory arrest, convulsions, and ventricular arrhythmias. Prevention is extremely important in poisoning therapy. Supportive measures are all that is generally needed for mild poisoning. Moderate and severe overdoses will require respiratory support, anticonvulsants, physostigmine, and beta-blockers. Cardioversion and pacing may be necessary.

Adolescent↗
PubMed1978

Effects of imipramine, nitrite, and dimethylnitrosamine on reproduction in mice.

Administration of the tricyclic dibenzazepine drug imipramine, a tertiary amine, in the food (100 mg/kg) or sodium nitrite (1 g/liter) or dimethylnitrosamine (0.1 ppm) in the drinking water of Swiss CD-1 mice before and during pregnancy, resulted in increased perinatal death of the offspring compared to controls. Administration of imipramine and nitrite together had no effect on perinatal survival, but instead resulted in infertility or delayed impregnation in some females. A biological synergism or in vivo chemical interaction of the two chemicals is suggested.

Animals↗
PubMed1976

[Interaction of tricyclic antidepressants with noradrenaline and 5-hydroxytryptamine in peripheral preparations of the rat].

The potentiation of the noradrenaline (NA) actions by antidepressant drugs was studied in vitro on the rat vas deferens and in vivo on the rat blood pressure. A new dibenzazepine compound, LM 208, and two antiparkinsonian drugs, orphenadrine and its demethylated derivative, were compared to well known antidepressants. The modification by all these agents of the rat uterus response to 5-hydroxytryptamine (5-HT) was also investigated. The possible use of these interactions as models for NA and 5-HT uptake inhibition is discussed.

Animals↗
PubMed1975

Treatment of Cataplexy with Clomipramine.

A new antodepressant drug, clomipramine hydrochloride, closely related to imipramine hydrochloride, was used to treat four patients suffering from cataplexy, sleep paralysis, and hypnagogic hallucinations. Attacks of cataplexy were associated with rapid-eye-movement (REM) electroencephalographic patterns. Cloripramine, in doses of 25 to 75 mg/day, completely stopped all attacks of cataplexy, sleep paralysis, and hypnagogic hallucinations within 48 hours of initial therapy. The patients have been free of symptoms for periods of 10 to 21 months. Side effects included impotence in the male patients, but no hematologic, cardiovascular, hepatic, or renal toxic effects were observed. Available evidence suggests that such drugs inhibit those brain stem systems that control the toxic components of REM sleep.

Adult↗
PubMed1976

Potentiation of the antidepressant action of clomipramine by tryptophan.

In a double-blind study of 24 patients with endogenous depressiona group treated with clomipramine hydrochloride (chlorimipramine) plus tryptophan was compared with a group treated with clomipramine plus placebo. The sum of the ratings for depressed mood, suicidal intent, depressive thought content, and anxiety showed a more rapid improvement in the former group, the difference being already significant after 12 days of treatment. On the other hand, the ratings for retardation decreased about equally in both groups during the three-week treatment period. Side-effect ratings showed no significant increase but seemed to be partly influenced by the improvement of depressive symptoms. Plasma levels of clomipramine appeared to reach a plateau within a few days, whereas the monodesmethylated metabolite continued to rise for a longer period of time, and reached considerably higher values than the parent compound. In the tryptophan group the degree of improvement seemed to be positively correlated to these levels, suggesting that further improvement might have been reached in some patients by increasing the dose of clomipramine. The levels of 5-hydroxyindoleacetic acid in the cerebrospinal fluid appeared to be reduced by clomipramine administration. This effect was prevented by the additional treatment with tryptophan.

Adolescent↗
PubMed1979

Clomipramine-induced mania in unipolar depression.

Manic behavior during randomly assigned treatment with clomipramine (chlorimipramine) or amitriptyline hydrochloride developed in seven of 50 hospitalized unipolar depressed patients. Six of the 25 clomipramine-treated patients became manic. Only one patient in the amitriptyline-treated group developed manic behavior. The switch into mania occurred at the mean age of 63, much later than the reported age of risk for mania. Significant correlations were observed between the age at onset of mania, the number of days of clomipramine treatment, and the duration of the manic episode. We hypothesize that such a switch into mania in unipolar patients is triggered by the psychopharmacological effect of clomipramine through an alleged change in activity of the central dopamine and serotonin systems.

Adult↗
PubMed1979

Novel antidepressants and the biogenic amine hypothesis of depression. The case for iprindole and mianserin.

The introduction of two tricyclic compounds (iprindole and mianserin) that are reported to have antidepressant properties but to be relatively devoid of effects on central amine neurotransmitter systems has raised questions about the amine hypothesis of depression and about the mechanism of action of tricyclics in general. In view of the importance of these questions, a critical review of both the clinical and pharmacological profiles of iprindole and mianserin was undertaken. Iprindole is a relatively weak inhibitor of both norepinephrine (NE) and serotonin, whereas mianserin possesses at least modest potency as an inhibitor of NE uptake. However, the evidence is as yet insufficient to prove the superiority of iprindole over placebo in the treatment of those depressions characterized by endogenous symptoms. In considering the pharmacological profiles of these two drugs together with their clinical profiles, the data are not inconsistent with the hypothesized role of biogenic amines in major depression.

Adjustment Disorders↗
PubMed1977

Monoamine metabolites in cerebrospinal fluid and serotonin uptake inhibition during treatment with chlorimipramine.

The effects of chlorimipramine on the concentrations of the main metabolites of serotonin (5-HT) norepinephrine (NE), and dopamine, i.e. 5-hydroxyindoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and homovanillic acid (HVA), respectively, were studied in cerebrospinal fluid from 14 depressed patients, and related to the serotonin- and NE uptake inhibiting activity in vitro of plasma drawn from the patients. Chlorimipramine inhibited the uptake of both transmitter amines in all patients. During treatment, the levels of 5-HIAA and HMPG in cerebrospinal fluid (CSF) were significantly reduced. HVA levels were reduced in 6 patients and increased in 8 patients; there was no mean change. The decrease in 5-HIAA level in CSF was correlated to the uptake inhibition of 5-HT but there was no corresponding relationship between NE uptake and HMPG levels. The changes in HVA levels were also correlated to the uptake of 5-HT despite the absence of a unidirectional change of this metabolite.

Biogenic Amines↗