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Biomedical subjects

Z Kleinrok

Publications and source records attributed to Z Kleinrok.

At least 343 records · Page 19Linked to original sources
PubMedDate not supplied

Effects of serotonin-active drugs on prolactin secretion in male rats.

The effects of several serotonin acting drugs on serum prolactin levels were studied in male rats. Administration of the serotonin precursor, 5-hydroxytryptophan (5-HTP; 250 mg/kg ip) or pargyline (5 mg/kg ip) with 5-HTP (100 mg/kg ip) significantly increased serum prolactin concentration. Pretreatment of rats with the serotonin agonist, quipazine (10 mg/kg ip) caused increase in serum prolactin levels. Depletion of serotonin stores by pretreatment with p-chloro-phenylalanine methyl-ester (PCPA; 3 x 300 mg/kg ip) significantly prevent the effect of quipazine on prolactin levels. Serotonin uptake blocker, fluoxetine (10 mg/kg ip) produces an increase in the prolactin concentrations of the serum. Administration of the reserpine (2.5 mg/kg sc) did not affect serum prolactin levels. Both serotonin receptor blockers, cyproheptadine (0.5 mg/kg ip) and pizotifen (1 mg/kg ip) caused a week decrease in the serum prolactin levels. Significant changes in concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brain of rats pretreated with above serotonin-active drugs were found. These results indicate that serotonergic system can modify secretion of prolactin.

Animals↗
PubMedDate not supplied

Synthesis and pharmacological properties of new derivatives of 1-diphenylacetamide-2-butanol.

Newly synthesized derivatives of 1-diphenylacetamide-2-butanol were investigated pharmacologically for their central properties in mice and rats. The most active were 2 compounds: racemic (RS) and enantiomer S (+) form of N-diphenylacetamide-2-butanol which produced hypothermia in normothermic mice, showed anxiolytic action in the four-plate test and reversed reserpine-induced hypothermia.

Acetamides↗
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Synthesis and pharmacological properties of diphenylimidazolidine acetic and propionic acids derivatives.

Several derivatives of diphenylimidazolidine-2,4-dione and diphenylimidazolidin-4-one acetic and propionic acids have been synthesized. Some of them were screened for their effect on the CNS in mice and rats. All the investigated compounds showed an analgesic activity. The most active one was 1-benzyl-5,5-diphenyl-3-imidazolidine-2,4-dione acetic acid. That compound exerted an inhibitory activity against the CNS, anxiety-relieving, anticonvulsant and antidepressive effects.

Acetates↗
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Preliminary pharmacological evaluation of chelidonine in rodents.

Our studies showed that the chelidonine administered intraperitoneally (ip) exerted an inhibitory effect on the central nervous system of the rodents. It was shown that chelidonine depressed the spontaneous and explorative motor activities, decreased body temperature, potentiated the action of hypnotics and increased sedation in reserpinized mice. Chelidonine did not affect the reactivity of the mice in the hot-plate test, and was without any protective effect against pentylenetetrazol-induced seizures. This alkaloid antagonized the head twitch response induced by 5-hydroxytryptophan (5-HTP) or 5-methoxytryptamine (5-MT) in the rat.

5-Hydroxytryptophan↗
PubMedDate not supplied

5-Methoxytryptamine-induced head twitches in rats.

In rats pretreated with pargyline ip injection of 5-methoxytryptamine (5-MT), but not of 5-HT, produced characteristic head twitches. 5-HT receptor blocking agents (cyproheptadine, methergoline, mianserine, WA-335-BS, and methsergide) reduced the effect of 5-MT. These substances in doses 20-160 times higher than their ED50 in head twitch test did not antagonize the pinna reflex. 5-MT-induced head twitches were also inhibited by imipramine, morphine, phenoxybenzamine and aceperone. However, their ED50 were only 3-8 times below the doses necessary to inhibit the pinna reflex. Reserpine, phentolamine, spiroperidol, pimozide and LiCl did not modify head twitches produced by 5-MT, while PCPA even potentiated them. Our results suggest the 5-MT-induced head twitches are due to the activation of the central 5-HT mechanisms probably as a result of direct stimulation of 5-HT receptors by 5-MT. Antagonism of 5-MT-induced head twitches and the dissociation of doses effective in this test from those inhibiting the pinna reflex may be of value in the prediction of central 5-HT receptor blocking properties.

5-Methoxytryptamine↗
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Some pharmacological properties and subacute and chronic toxicity of tryptamide.

Studies on Albino Swiss mice and Wistar rats have demonstrated that tryptamide is less ulcerogenic than phenylbutazone, and markedly inhibits intestinal peristalsis. Both compounds have a similar tendency to accumulate in the body. Tryptamide produces a smaller hypotension and stimulates the respiratory amplitude to a lesser extent than phenylbutazone in a vivisectional experiment. Studies on the subacute and chronic toxicity have demonstrated that tryptamide administered orally (po) and intraperitioneally (ip) for 3 weeks, and orally for 3 months neither affects the body weight gain or the mass of internal organs, nor changes the locomotor activity; only in rats it disturbs the motor coordination. After ip administration tryptamide shows a moderate depressant effect on the bone marrow, evidenced by a decline in the blood hemoglobin content and the number of erythrocytes and blood platelets. As those changes were more pronounced after a 3-week than a 3-month administration, the observed effects are apparently reversible.

Animals↗
PubMedDate not supplied

Effects of electroconvulsive shock on central GABA-ergic mechanisms.

A single electroconvulsive shock (ECS) has no influence on seizures induced by picrotoxin and bicuculline, although it decreases the level of GABA in the cortex. A repeated ECS (once daily for 7 days) does not change the level of GABA in the cortex, brain stem, and cerebellum, but depresses seizures induced by both compounds. It prolongs the time of their occurrence and decreases their intensity. This effect is stronger in the case of bicuculline. It manifests itself in the increase of the number of animals protected from seizures and decrease of their lethality. Baclofen does not change ECS action on seizures induced by picrotoxin and bicuculline whereas it enhances catalepsy caused by ECS. Bicuculline does not change the time-course of catalepsy. The obtained results suggest that repeated ECS reduces the seizures induced by GABA antagonists probably y increasing GABA-ergic transmission or/and by increasing dopaminergic and serotoninergic transmission which significantly modify the activity of GABA-ergic neurons.

Animals↗
PubMedDate not supplied

Preliminary pharmacological investigation on 38 aminophosphonic acids and their derivatives.

Central pharmacological properties of 38 aminophosphonic acids and their derivatives, mostly newly synthesized, were investigated on mice and rats. Acute toxicity, neurotoxic activity, influence on spontaneous locomotor activity, body temperature, electrogenic and pentetrazol convulsions, on cerebral GABA level were tested. The most active compounds were (in a decreasing order of activity): 2-amino-7-phosphonoheptanoic, 2-amino-5-phosphonovaleric, 2-amino-8-phosphonooctanoic, 2-amino-2-methyl-3-methylphosphonopropionic, and 3-amino-3-hydroxy-5-phosphonovaleric acid.

Amino Acids↗
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A role of some central neurotransmitter systems in the mechanism of electroconvulsive shock action.

Behavioral effects of electroconvulsive shock (ECS) on the neurotransmitter systems were studied in relation to the mechanism of action. Repeated ECS, applied to rats, enhanced the behavioral response to dopaminergic, serotonergic and opiate agonists and attenuated the behavioral effects to GABA-ergic antagonists. The same ECS schedule did not significantly alter the behavioral response to alpha 2- and beta-adrenergic agonists and apomorphine-induced stereotypy but significantly potentiated haloperidol-induced catalepsy.

Animals↗
PubMedDate not supplied

Inhibition by antiepileptics of carbachol but not lithium- or 5-methoxytryptamine-induced wet dog shakes in rats.

The influence of antiepileptic drugs on the wet dog shakes (WDS) induced by intracerebroventricular injections of carbachol (30 micrograms icv) was investigated in rats. Diphenylhydantoin (DPH, 8 and 4 mg/kg), diazepam (0.4, 0.2 and 0.1 mg/kg), phenobarbital (12.5, 6.25 and 3.12 mg/kg), sodium valproate (Depakine, 200, 100 and 50 mg/kg) and trimethadione (200, 100 and 50 mg/kg) given ip inhibited the WDS in a dose-dependent manner. These drugs at the same doses did not change the intensity of shaking behavior induced by lithium chloride or 5-hydroxytryptamine. As the antiepileptic drugs tested in these experiments did not have anticholinergic activity and at used doses were not able to prevent electrical convulsions or pentetrazol-induced seizures, it appears that carbachol-induced WDS could be connected with convulsive activity and could be the initial stage of seizures.

5-Methoxytryptamine↗
PubMedDate not supplied

Opiate-like peptides. Part XI. 2-[2-phenyl-1,3-indandionyl]--amides of enkephalin analogs. Synthesis and analgesic activity.

Four enkephalin analogs containing C-terminal 2-amino-2-phenyl-1,3-indandione residue were prepared: [Met-NHPID5]--enkephalin (E3), [D-Ala2,Met-NHPID5]--enkephalin (E4), [Leu-NHPID5]--enkephalin (E5), [D-Ala2,Leu-NHPID5]--enkephalin (E6). Their analgesic activities were assayed by three in vivo tests: the "hot plate" method, the reaction to electric painful stimulus and the writhing syndrome test. Neurotoxicity effects were determined by the rota-rod test. The most pronounced analgesic effect was induced by compounds with D-Ala in position 2, particularly in the "hot plate" test.

Animals↗
PubMedDate not supplied

Central action of sanumgerman administered orally in mice.

The behavioral and biochemical studies showed that daily oral administration of sanumgerman (340 mg/kg, i.e. 1/5 LD50) for 3 days exerted a depressive influence on the central nervous system of the mouse. The mechanism of this action could be related to an inhibition of catecholaminergic and of serotoninergic central system activities.

Administration, Oral↗
PubMedDate not supplied

The effect of frontal cortex lesion on the activity of the dopaminergic system in rat striatum.

The experiment was carried out on male Wistar rats weighing 180-220 g with lesion in the cortex of the frontal lobe. The activity of the dopaminergic system was studied by means of behavioural tests such as determination of spontaneous motor activity, apomorphine-induced stereotypy, haloperidol-induced catalepsy. Increased intensity of stereotypy was observed reaching a maximum 14 days after frontal lobe damage. Moreover, a slight tendency was observed for inhibition of haloperidol-induced catalepsy without changes in the spontaneous motor activity of the animals. Biochemical investigations demonstrated reduced dopamine content in the striatum on the side of the lesion.

Afferent Pathways↗
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The effect of repeated administration of insulin on pain threshold and gamma-aminobutyric acid level in mouse brain.

In experiments on male Albino-Swiss mice weighing 18-22 g insulin given in doses of 2 i.u./kg caused no change in the time of reaction to pain, while the same dose administered daily for 7 days potentiated the analgesic action of morphine (3 mg/kg s.c.). Glucose caused no change in this effect of insulin. After 14 days of insulin treatment the time of reaction to pain in the animals subjected to the action of morphine returned to its initial value. Twenty-four hours after the last administration of morphine the level of gamma-aminobutyric acid (GABA) was found to be decreased in the animals receiving insulin with glucose. These results suggest that the central action of insulin is dependent not only on hypoglycaemia produced by it, but may be due also to its direct action on the central structures and an indirect action mediated by its effect on other neurotransmitter systems.

Animals↗
PubMedDate not supplied

The seizures induced by pilocarpine: behavioral, electroencephalographic and neuropathological studies in rodents.

Seizures produced by systemic administration of pilocarpine hydrochloride, a cholinergic muscarinic agonist, in rodents are proposed as a useful animal model of epilepsy. Pilocarpine-induced seizures in rats and mice are characterized by sequential development of behavioral and electrographic signs, which are followed by widespread damage to the forebrain (hippocampus, amygdala, thalamus, olfactory cortex, neocortex and substantia nigra). Spontaneous seizures may be observed in the long-term period following the administration of convulsant doses of pilocarpine. In experiments designed to examine neuronal networks engaged in the generation and spread of pilocarpine-induced convulsions, a marked role for the basal ganglia is demonstrated. The caudate-putamen, the substantia nigra and the entopeduncular nucleus were found to govern the propagation of seizures produced by pilocarpine. The antiepileptic potential of drugs (diazepam, clonazepam, phenobarbital, valproic acid and trimethadione) against pilocarpine-induced convulsions correlates with their depressant action on the spontaneous activity of non-dopaminergic cells in the substantia nigra. Developmental studies show age-dependent differences in the convulsant response of rats to pilocarpine and status epilepticus are first noted in 2-3 week-old rats, but there is no clear-cut correlation between seizures and evolution of brain damage at this age. The adult pattern of the damage to forebrain is seen after a delay of 1-2 weeks relative to the development of seizures and status epilepticus. The research on the pilocarpine model of convulsions and other cholinergically mediated seizure syndromes may be of value for designing new therapeutic approaches to epilepsy in.

Animals↗
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The effect of alpha-adrenergic receptor stimulant drugs on amphetamine or apomorphine-induced stereotypy in rats.

Clonidine, xylometazoline and naphazoline given ip cause a transition from sniffing to licking or gnawing stereotypy induced by amphetamine or apomorphine. Methoxamine, phenylephrine and in a lesser degree noradrenaline (all given ivc) inhibit licking and gnawing stereotyped behavior. Biochemical results correlate with the depressant action of clonidine and naphazoline on central noradrenergic neurotransmission and also with the stimulant action of methoxamine and phenylephrine on noradrenergic system. The both groups of alpha-adrenergic agonists seem to modify both the central dopaminergic and noradrenergic system activity in the same direction. It is suggested that this action can play a role in observed modification by alpha-sympathomimetic drugs of responses to dopamine agonists. However, the influence of alpha-sympathomimetics on other brain systems must be also taken into consideration.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Synthesis and search for anticonvulsive and hypoglycemic properties of novel 5-benzylidene derivatives of 3-o-chloro- and 3-o-methylbenzoyl-2-thiohydantoin.

14 new benzylidene derivatives of 3-o-chloro- and 3-o-methylbenzoyl-2 thio hydantoin were synthesized. Their chemical structure was confirmed by IR, NMR and mass spectroscopy. Compounds 1-14 were tested for their anticonvulsant and hypoglycemic activity. Their toxicity was low and they showed only weak activity in tests for anticonvulsive and hypoglycemic properties.

Animals↗