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Pharmacological properties of new neuroleptic compounds.
Metadata
JournalArzneimittelforschungNot FoundDate
1975-Sep
Publication Type
Journal Article
Comparative Study
Volume
1975-Sep / 25 : 1436-42
Author
Coscia L , Causa P , Giuliani E , Nunziata A
Doi
Not Found
PMIDMESH
Aggression
Amphetamine
Animals
Apomorphine
Avoidance Learning
Behavior, Animal
Blood Pressure
Chlordiazepoxide
Chlorpromazine
Dibenzoxepins
Drug Evaluation, Preclinical
Epinephrine
Guinea Pigs
Histamine H1 Antagonists
Humans
Lethal Dose 50
Male
Mice
Motor Activity
Muscle Contraction
Piperazines
Rats
Sleep
Time Factors
Tranquilizing Agents
Abstract
RMI 61 140, RMI 61 144 and RMI 61 280 are newly synthetized N-[8-R-dibenzo(b,f)oxepin-10-yl]-N'-methyl-piperazine-maleates which show interesting psychopharmacologic effects. This work contains the results of a study performed with these three compounds, in order to demonstrate their neuropsycholeptic activity in comparison with chloropromazine (CPZ) and chlordiazepoxide (CPD). The inhibition of motility observed in mice shows that the compounds reduce the normal spontaneous motility as well as the muscle tone. The central-depressant activity is evidenced by increased barbiturate-induced sleep and a remarkable eyelid ptosis can also be observed. Our compounds do not show any activity on electroshock just as do CPZ and CPD. As to the antipsychotic outline, our compounds show strong reduction of lethality due to amphetamine in grouped mice and a strong antiapomorphine activity. They show also an antiaggressive effect and an inhibitory activity on avoidance behaviour much stronger than CPZ. We have also found extrapyramidal effects, as catalepsy, common to many tranquillizers of the kind of the standards used by us. As for vegetative phenomena, the compounds show hypotensive dose related action ranging from moderate to strong, probably due to an a-receptor inhibition. Adrenolytic activity against lethal doses of adrenaline, antiserotonin and antihistaminic effects, as well as other actions (hypothermia, analgesia, etc.) confirm that RMI 61 140, RMI 61 144 and RMI 61 280 are endowed with pharmacologic properties similar and more potent than those of CPZ. Studies on the metabolism of brain catecholamines show that they are similar to CPZ, although with less effect on dopamine level.
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