International journal of neuropharmacology最新文献

The effect of oxotremorine upon the incorporation of³H-leucine into subcellular fractions has been investigated in two regions of the rat CNS, and a significant increase in protein synthesis has been demonstrated during the acute phase of oxotremorine-induced functional activity. The tissue concentration of free labelled amino acids was slightly decreased at this time thus eliminating an alteration in the free amino acid pool as a possible causative factor. There was no increase of isotope incorporation into liver proteins during the same period.

Repeated stimulation with this powerful tremorogenic drug did not change the turnover of proteins in the striatum or in the gray matter of the spinal cord.

The effect of HS-2314, a new psychosedative drug, was determined in unanesthetized, unrestrained cats and rabbits. The effect was measured by the use of several electro-physiological techniques and behavioural observations. A comparative study with chlordiazepoxide, diazepam and chlorpromazine was performed.

It was found that HS-2314 reduced aggressiveness in cats, abolished the amygdala spindles induced by presentation of a rat and evoked synchronization of the EEG in several cortical and subcortical structures. HS-2314 seems to be clearly differentiated from diazepam, chlordiazepoxide and chlorpromazine.

The central actions of the pemolinic base of magnesium upon the brain mechanisms involved in sleep and wakefulness were studied in cats with electrodes and cannulae permanently implanted in the brains. It was found: (1) that this drug increases the excitability of the vigilance system producing the corresponding changes in the electrical activity of the neocortex and of the olfactory bulb in the intact animal, but not in the animal with a lesion in the mesencephalic tegmentum. (2) that this drug counteracts both spontaneous sleep as well as sleep induced by cholinergic stimulation of the hypnogenic central pathways.

It is suggested that the antihypnic action of the pemolinic base of magnesium results from pharmacological interference of the inhibitory action that the sleep system tonically exerts upon the vigilance system.

A study has been made of some pharmacological actions of tertiary amine analogues of drugs known to be active in the quaternary salt form. Tertiary amine analogues of acetylcholine, carbachol,m-bromophenyl-2-dimethylaminoethyl ether methobromide, neostigmine, hexamethonium and 4-dimethylamino-methyl-2-methyl-1,3-dioxolane methiodide were prepared and tested pharmacologically.

It was found that the presence of a quaternary ammonium group was essential for high muscarinic activity in acetylcholine, carbachol and the dioxolane and also for cholinesterase inhibiting activity in neostigmine. Tertiary amine analogues of acetylcholine retained some nicotinic activity at the neuromuscular junction and also some cholinesterase substrate activity. Nicotinic activity at the neuromuscular junction or at autonomie ganglia was not retained by the pyrrolidine analogue ofm-bromophenyl-2-dimethylamino ether methobromide. The pyrrolidine analogue of carbachol was similarly inactive at the neuromuscular junction but showed weak ganglion-stimulating activity. In the hexamethonium series quaternary salts and tertiary bases did not differ greatly in ganglion-blocking potency.

The active tertiary amines were tested for behavioural effects in the open-field test but no evidence for appreciable central activity was found.

The effects of strychnine on the inhibition of spinal interneurons produced by glycine and GABA was studied by means of iontophoretic application from multibarrel electrodes. The actions of glycine were more effectively blocked by strychnine than were those of GABA. The data suggest that a non-competitive type of antagonism exists between strychnine and these inhibitory amino acids.

When mice were exposed to a revolving drum stress (42 rev/min) for a few minutes, a biphasic effect on the latency to tonic extension following a supramaximal electroshock seizure was observed. A two-fold increase in the time to seizure was seen immediately after stress which was followed by a return to control values within 10–15 min. Beginning 15 min later, a second increase in latency occurred which persisted for several hours. No change on the biphasic response pattern was observed if mice were given chlorpromazine or dibenamine prior to stress, or were bilaterally adrenalectomized 4 days prior to study. Reserpine, given in a dose which reduced the latency to tonic extension in non-stressed mice, was found to antagonize both phases of the increased latency seen after drum stress. Catecholamine or corticosteroid release could not be implicated to explain these findings.

Cortical visually evoked responses (VER) elicited by electrical stimulation of the ipsilateral optic tract were dramatically facilitated by stimulation of the midbrain reticular formation. This facilitation depended on the experimental conditions used, such as the intensity and time course of reticular (RFs) and optic tract stimulation (OTs). Reticular facilitation of the VER was most intense at 8 times the EEG activating threshold with a 50 msec interval between the RFs and OTs. The effects of increasing accumulative doses of pentobarbital, ethyl alcohol, and chlorpromazine given i.v. on reticular facilitation of the VER were observed. In general. these agents did not alter the presynaptic component of the VER except for 32 mg/kg of pentobarbital which increased it. On the other hand, pentobarbital had a marked depressant effect on both the cortical postsynaptic components and relicular influences on them. However. pentobarbital did not depress reticular facilitation of the VER as much as the non-facilitated VER. This data would suggest that pentobarbital has a neocortical depressant effect which is somewhat greater than its effect on the midbrain reticular formation. Ethyl alcohol had a similar cortical depressant effect but produced no significant depression of reticular facilitation of the VER. In fact, RFs restored the VER almost to control. Chlorpromazine (0.5 mg/kg, i.v.) reduced slightly the cortical postsynaptic components of the VER but had no effect on its facilitation by RFs.

These results suggest that reticular facilitation of the VER is more resistant to depression by pentobarbital and ethyl alcohol than the VER alone. The postsynaptic components of the VER are quite sensitive to the effects of these drugs in contrast to its presynaptic component. In marked contrast to the actions of pentobarbital and ethyl alcohol, chlorpromazine showed much less of a postsynaptic neocortical depressant effect even when massive doses (up to 16 mg/kg) were used.