566 The neuroplegic effect of frenolon, a new phenothiazine compound

Abstracts of Papers characteristic way by intravenous administration of small doses of largactil (0.2-0.3 mg/kg) : (a) Afternystagmus is considerably enhanced : (b) The decay of the response under high frequency stimulation’*’ is delayed or completely abolished: and (c) The maintenance of a uniform, persistent reaction during intermittent stimulation is grratly improved. The effects can bc tentatively explained by assuming either a selective suppression of the inhibitory components of the nystagmus mechanism or a specific facilitation in reverberating circuits.

1. LACHMANN, J., BER~MANN, F. and MONNIER, M. (1958), Amer. 3. Physiol..193, 328. 2. BERGMANN, F., LACHMANN, J., CHAIMOVITZ, M. and CUTMAN, J. ( 1961 j, Exptl. ,Veurol.. 3,487. 566 The Neuroplegic Effect of Frenolon, a New Phenothiazine Compound. J. BORSY and L. TOLDY (Hungary). \Te made investigations into the neuro-sedative and toxic actions of the abovc compound and compared thr results with those exhibited by chlorpromazine, prrphenazine and thiopropazate, respectively. With intraperitoneal or peroral administration in mice, Frenolon strongly inhibits the hyperactivity due to the orientational reflex. Its 50 per cent inhibitory dose (ED,,) amounts to 0.23 mg/kg i.p. thus being 6.07 times as active as chlorpromazine By the oral route Frenolon proved in this respect. to be 3.1 times as active as chlorpromazine, it exceeded the activity of perphcnazine and nearly equalled thiopropazate. \Vhen using Schlichtegroll’s method, Frenolon rxerted strong cataleptic action, its 50 per cent cataleptic dose (ED,,) being as high as 5 mg/kg per OS in the mouse. Concerning its catalepsy producing efficacy, this is somewhat higher than the other phenothiazine derivatives rxamined by us. By means of Burn’s method, Frenolon, in doses of 2.5-5.0 mg/kg by mouth, diminished the toxicity of benzopropamine. The hypermotility state evoked by this excitant drug in mice was depressed by an i.p. dose of 0.25 mg/kg of Frenolon (60 per cent inhibitory efhect), whereas chlorpromazine was able to inhibit only to 46 per cent in a dose of 1.0 mg/kg. Frenolon potentiates Hexobarbital anaesthesia in rats to the same extent as perphenazine or thiopropazate. Its hypothrrmic effect is weaker than that of both the latter drugs. Frenolon seems to possess low grade, acute and chronic toxicity by intravenous and peroral administration, respectively. 567 On the Relation between the Ataractic and Some Other Types of Central Action of Some Phenothiazine Derivatives. B. I. LIUBIMOV and K. S. RAEVSKY (U.S.S.R.). This work has been undertaken

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comparing various aspects of central action exerted by neuroplegic drugs of the phenothiazine group by means of an assessment of the intensity of such The intention was effects exerted by each agent. also to find out whether any parallelism existed between the ataractic, the anticonvulsant, the central muscle-relaxant and the hypothermic effects Aminazine, propazine, acetazine, of these agents. mepazine, metcrazine and etaperazine were the objects of this study. Luminal, possessing a marked depressing cffcct on central nervous system. was \Vhite mice and chosen for the sake of comparison. The espcrirats served as experimental animals. ments have shown that etaperazine and meterazine possess the most marked ataractic effect, propazinc and mepazine the leant. with acetazine and aminazinc occupying an intrrmcdiatr position. Luminal, according to our data products no ataractic effect. The anticonvulsant effect was equally marked in propazine, aminazine, acctazinc and mepazine. Meterazine and etaperazinc possess lo\\ activity in this respect. Central relaxant action x$as most pronounced with acetazine and aminazine, next with etaperazine and meterazinc while propazine and mepazine were least active in this rcspcct. Hypothermic action of the above agents in doses corresponding to ED,, of the ataractic effect manifested itself in the following manner: the grcatcst temperature drop (7 ) was seen after administration of acetazine and propazinc: aminazine and mepazinc depressed the body temperature of animals by 3-4’; and, finally, meterazine and ctaperazinr in the above doses were practically unaccompanied by any hypothermic rlfect. In doses corresponding to ED,” of the muscle relaxant effect. propazine, aminazine, mcpazinc and acctazinr producrd considerable hypotoermia: body tcmperaturr of animals dropped by 7 11.. hleterasine and ctapcrazinc produced a drop of 2.5-4.; Summarizing our data. one may conrludc that in some of the substances (etaperazinc and meterazinr) the ataractic effect is pronounced, thr anticonvulsive action is practically absent. and the hypothermic and the central rzlasant cflccts are moderatc. In others (mcpazine and propazincl the anticonvulsive action is intense. \vhile the ataractic and the muscle relaxant effects are much weaker than in the related substances. The results obtained show that in this scrics of phenithiazine drrivati\cs no parallelism csists between the various type of central action studied. 568 On the Influence of the Neuroplegic Drugs on Chemoreception. U. I. VIKHLIAEV (U.S.S.R.). The author studied the influence of a number of phenothiazine derivatives, aminazinr. mepazine, propazine and etaperazine (Trilafon), administered intravenously and intraarterially, on the sensitivity of the blood vessels in the hind-leg to acetylcholine and NaCl. Experiments were carried out on anaesthetized cats (uretrane, urethane with chlorat), using the method of vascular isolation of the lower