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PubMed1975

Neuroleptic piperazinyl-dibenzo-azepines. Chemistry and structure-activity relationships.

The chemistry and the molecular and physicochemical properties of the 11-piperazinyl derivatives of dibenz[b,f][1,4]-oxazepines and -thiazepines and of dibenzo[b,e][1,4]diazepines as well as those of the 6-piperazinyl-morphanthridines are reviewed. The physicochemical parameters sigma, pK, eta, RM and surface pressure are considered in relation to each other and in relation to two pharmacological effects, namely apomorphine antagonism and cataleptic activities. The influence of substituents, bridging moiety and basic side chain on structure-activity are discussed. Finally, the dibenzodiazepine derivative clozapine, which differs markedly from the classical neuroleptics in its biochemical, pharmacological and clinical properties and represents a new type of antipsychotic agent, is discussed.

Animals↗
PubMed1985

[Clinico-electrophysiologic studies on the action of the anti-arrhythmic substance 3-carbethoxyamino-5-dimethylamino-acetyl-10,11-dihydro-5H- dibenz[b,f]azepine hydrochloride (Bonnecor, AWD 19-166, GS 015)].

The effects of the new antiarrhythmic drug 3-carbethoxy-amino-5-dimethyl-amino-acetyl-iminodibenzyl-hydroc hlorid (Bonnecor) (B.) were investigated by means of clinical-electrophysiologic methods (His-bundle electrography, programmed electrical stimulation) in 11 patients with normal cardiac output and paroxysmal supraventricular tachycardias. In a maximal dosage of 0.24 mg/kg body mass. B. affects several compartments of the impulse initiation and conduction. B. has positive chronotropic actions on the sinus node automaticity, negative dromotropic effects on the sinu-atrial, intraatrial, AV nodal and intraventricular conduction and finally negative bathmotropic actions on the myocardium of the atria and ventricles. B. suppress the artificial induction of paroxysmal supraventricular tachycardias in patients with AV nodal reentry. These results help to recognize indications (supraventricular and ventricular premature beats or tachycardias) and contraindications (sick sinus syndrome, atrio-ventricular block of higher degreé and bifascicular blocks).

Adult↗
PubMed1985

[Antiarrhythmic effectiveness of 3-carbalkoxyamino-5-(omega-aminoacyl)-10,11-dihydro-5H-dibenz-[b,f]- azepines].

The derivatives of a novel structure series of dibenzazepines dispose of intense antiarrhythmic properties. The relations between structure and effect in comparison with the antiarrhythmically active derivatives of phenothiazine (Ethmozine) are discussed. When substituting the beta-aminopropionyl chain with cyclic residue by means of a dimethylaminoacyl chain there appears a marked antifibrillatory action besides of the intense antiarrhythmic one. The compound 17, the 3-carbethoxyamino-5-dimethylaminoacetyl-dibenzazepine, proved to be the most efficacious compound in the course of the basic screening on two models: action on the effective refractory period in the rabbit's atrium and aconitin-induced arrhythmia in the conscious rat. In comparison with Ethmozin, an antiarrhythmic agent of the phenothiazine type, 17 shows a somewhat lower efficacy in case of i.v. application, but a distinctly intenser one was stated after oral administration. A profound test on the models: two-step coronary ligature in the dog according to Harris and electrofibrillation in the cat's heart, revealed an equally intense antiarrhythmic action but a considerably intenser antifibrillatory one. Therefore the compound 17 (abbreviated designation in the USSR: GS 015 or in the GDR: AWD 19-166) was provided for a thorough pharmacological and toxcological study.

Animals↗