Effects of some benzodiazepine derivatives on fibrinolysis and serum lipids in normolipidaemic rats and in humans.
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Biomedical subjects
Publications and source records attributed to B Cuparencu.
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In experiments with rats and mice it was been found that centrophenoxine in acute experiments in large doses has inhibitory effects on the central nervous system. Centrophenoxine has no analgesic action. When administered subchronically, centrophenoxine aggravates both the pentetrazol and the maximal electroshock seizures.
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Apomorphine administered in reserpine-induced as well as in restraint ulcers in rats, failed to afford protection. Pimozide, moperone, trifluperidol and chlorpromazine fail to influence the development of the experimental ulcers. Pimozide and moperone although antagonizing the behavioral changes of amphetamine, maintained its antiulcer activity. Amitryptiline, cocaine and morphine had a protective activity. L-Dopa afforded a significant protection which was abolished if this compound was administered together with FLA-63, a specific dopamine-beta-hydroxilase inhibitor. These results were explained by admitting that not dopamine, but noradrenaline was responsible for the antiulcer activity. alpha-Methyl-dopa produced a significant protection in both experimental models.
In reserpine-induced ulcers in rats, the centrally acting sympathomimetic ámines (amphetamine, mephentermine and ephedrine) produced a significant protection. Only amphetamine had a beneficial effect in restraint ulcers. Tyramine, a preponderant peripherally acting sympathominetic amine, was inefficient in both experimental models. It is suggested that the protective activity is due to the influence of these amines on the adrenergic structures, mainly at central level.
Chlorpromazine (CPZ) a neuroleptic which has both antiadrenergic and antidopaminergic activity when administered in doses of 5 to 25 mg/kg s.c. inhibited ovulation and induced pseudopregnancy. Pimozide which possesses only an antidopaminergic action induced only pseudopregnancy (in doses between 0.05-10 mg/kg s.c.). Apomorphine (APO), a dopaminergic agonist, prevented the pseudopregnant effect of both neuroleptics, especially of CPZ, but failed to counteract the ovulation-blocking action of CPZ. APO itself had an antiovulatory action, but only in large doses (above 5 mg/kg s.c.), and only in a few animals. Our data plead for the importance of dopaminergic mechanisms in the inhibition of prolactin secretion (by means of PIF) and for the stimulatory role of adrenergic transmission in the ovulation process (by means of LRF). These results fail to support the proposed stimulatory role of dopamine on the LRF secretion. On the contrary, they do not exclude the possibility of its inhibitory action.
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Amphepramone, an anorectic agent, has been found to possess stimulant properties on the C.N.S. in animals, producing hypermotility and stereotyped movements which can be antagonized with neuroleptics. The stimulant activity of amphepramone observed in animals can be correlated with the amphetamine like psychosis observed in humans.
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In experiments carried out in mice, it was shown that amantadine (adamantine) (50, 75, 100 and 200 mg/kg i.p.) reduced the exploratory activity. This phenomenon was due not to reduction of the locomotion and of the muscular force. Amantadine in large doses had a slight convulsant action; at the same dose (100 mg/kg i.p.) it greatly potentiated the convulsant effects of pentetrazol. On Haffner's test amantadine had no analgesic activity.
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