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Biomedical subjects

G Skuza

Publications and source records attributed to G Skuza.

At least 55 records · Page 3Linked to original sources
PubMed1983

The effect of selective inhibitors of noradrenaline and serotonin uptake on reserpine- and apomorphine induced hypothermia in mice.

The antidepressant action of combined treatment with selective inhibitors of noradrenaline (NA) and serotonin (5HT) uptake was investigated using the reserpine and apomorphine hypothermia tests. Desipramine and maprotiline, NA uptake inhibitors, but not fluoxetine and citalopram, selective 5HT uptake inhibitors, antagonized the hypothermias. A combination of NA and 5HT uptake inhibitors antagonized reserpine hypothermia less effectively than the inhibitor of NA uptake alone. The apomorphine hypothermia was antagonized similarly by a NA uptake inhibitor given alone and in combination with a 5HT uptake inhibitor. The results indicate that for antidepressant (antireserpine and antiapomorphine) effect the essential role is played by a noradrenergic mechanism, while the serotonergic mechanism may even produce opposite effect.

Animals↗
PubMed1982

Fluvoxamine, a new antidepressant drug, fails to show antiserotonin activity.

Fluvoxamine, (E)-5-methoxy-4'-(trifluoromethyl)valerophenone O-2(2-aminoethyl)oxime, a new antidepressant drug inhibiting serotonin (5-HT) uptake, was studied in rats and mice in order to check whether it has any central anti-5-HT activity, as do some tricyclic antidepressants, e.g. amitriptyline and doxepin. Fluvoxamine did not influence either the 5-hydroxytryptophan-induced head twitch response in mice or the tryptamine convulsions in rats. In the hind limb flexor reflex of the spinal rat the stimulation induced by fenfluramine was inhibited, that induced by LSD was not changed. Fluvoxamine also antagonized the hyperthermia (at ambient temperature of 28 degrees C), induced in rats by fenfluramine or p-chloroamphetamine. The hyperthermia caused by m-chlorophenylpiperazine was not inhibited. Fluvoxamine did not antagonize the 5-HT pressor effect in pithed rats. It has no effect on the immobility time in the behavioural despair test in rats. The results indicate that fluvoxamine fails to show anti-5-HT activity.

5-Hydroxytryptophan↗
PubMed1982

Effects of chronic treatment with antidepressants on aggressiveness induced by clonidine in mice.

It has previously been found that a number of typical and atypical antidepressants, given chronically, intensify clonidine-induced aggressiveness in mice. Further experiments now show that chronic, but not acute, administration of nisoxetine, a selective inhibitor of noradrenaline uptake, potentiates clonidine-induced aggressiveness. Citalopram and fluvoxamine, two selective inhibitors of serotonin uptake, have no such action. Of the two isomers of flupenthixol, only the trans-form potentiates clonidine-induced aggressiveness of chronic experiments. The cis-form induces an inhibiting effect. Clonidine-induced aggressiveness is also intensified by chronic, but not by acute, administration of pizotifen, an antagonist fo serotonin and noradrenaline. The results seem to support the previous hypothesis that potentiation of clonidine-induced aggressiveness is mediated by an alpha 1-adrenergic mechanism.

Aggression↗
PubMed1982

Histidine-induced bizarre behaviour in rats: the possible involvement of central cholinergic system.

Histidine injected intraperitoneally into rats in doses from 400 to 800 mg/kg induced a dose-dependent bizarre behaviour. The behaviour after histidine was similar to that observed after L-DOPA and peripheral decarboxylase inhibition. The bizarre behaviour was antagonized by chloropyramine, ketotifen, clemastine and promethazine, antagonists of histamine H1 receptors, with ED50's of 13.9, 14.2, 21.6 and 22.2 mg/kg, respectively. Cimetidine, an antagonist of histamine H2 receptors, injected intraventricularly at a dose of 100 micrograms, was without effect. The bizarre behaviour after histidine was not changed by antagonists of dopamine, noradrenaline and serotonin receptors, but it was blocked by atropine, indicating involvement of central cholinergic systems.

Animals↗
PubMed1982

Central action of amitriptyline N-oxide.

The central action of amitriptyline N-oxide (AMINO) has been compared with amitriptyline (AMI) in biochemical and pharmacological studies in rats and mice. It has been found in rats that both drugs prevent 6-OH-dopamine-induced depletion of brain noradrenaline (NA). At the same time AMINO increases and AMI lowers the NA level, both being without effect on 3-methoxy-4-hydroxyphenylglycol concentrations in the brain. AMINO and AMI potentiate the depletion of 5-hydroxytryptamine (5-HT) induced by p-chloroamphetamine in the rat brain and it may be considered as evidence that both drugs do not inhibit 5-HT uptake in vivo. Neither AMINO nor AMI affects the rat brain level of 5-HT but at higher doses they elevate the 5-hydroxy-indoleacetic acid concentrations. AMINO antagonizes the head twitch reaction induced by 5-hydroxytryptophan in mice and tryptamine convulsions in rats. The hyperthermia induced by fenfluramine (in rats at a high ambient temperature) as well as the stimulation of the hind limb flexor reflex in spinal rats, induced by fenfluramine or LSD, are also inhibited. AMINO antagonizes the 5-HT-induced increase in blood pressure in pithed rats. All the above effects are similar to those induced by AMI, only the active doses of AMINO are higher. The results presented indicate that AMINO, like AMI, inhibits NA uptake and is a 5-HT antagonist.

5-Hydroxytryptophan↗
PubMed1981

Effects of antihistaminic drugs in tests for antidepressant action.

Antihistaminics of various chemical structures: chlorcyclizine, chloropyramine, chlorpheniramine, clemastine, diphenhydramine, mepyramine, promethazine, and thenalidine were investigated for the action in tests for antidepressant drugs. The antihistaminics did not affect significantly the spontaneous locomotor activity of rats. Most of them (chloropyramine, chlorpheniramine, diphenhydramine, promethazine and thenalidine) increased amphetamine hypermotility but chlorcyclizine significantly inhibited, and clemastine and mepyramine did not affect it. In mice, chlorcyclizine, mepyramine and promethazine inhibited amphetamine hypermotility, while others antihistaminics were without effect. L-DOPA-induced hypermotility in mice was inhibited by all compounds tested. With the exception of chlorpheniramine and mepyramine, all tested antihistaminics produced hypothermia in mice, although fife of them (chlorpheniramine, diphenhydramine, chlorcyclizine, chloropyramine and thenalidine) antagonized the reserpine-induced hypothermia. With the exception of mepyramine and clemastine, the compounds tested shortened the period of immobility of rats in the behavioral despair test. The results indicate that only few antihistaminics have pharmacological profile resembling tricyclic or atypical antidepressant drugs.

Amphetamine↗
PubMed1981

The effect of the antihistaminic drugs on the central action of 5-hydroxytryptophan in mice.

Antihistaminic drugs of various chemical structure (chlorcyclizine, chloropyramine, chlorpheniramine, clemastine, diphenhydramine, mepyramine, promethazine, thenalidine) were tested on their action on the central serotonin system in mice. The test used was the antagonism to behavioral syndrome produced by D, L-5-hydroxytryptophan (5-HTP). Clemastine, promethazine and thenalidine inhibited 5-HTP-induced syndrome in doses of much lower than those inhibiting locomotor activity. Similar but weaker effect was produced by chlorcyclizine and diphenhydramine. It could be suggested that these compounds exert central antiserotonergic action. Chloropyramine and, more strongly, chlorpheniramine potentiated the action of 5-HTP; this may be due to the inhibition of serotonin uptake. Only mepyramine in these tests did not show any action on the central serotonin system.

5-Hydroxytryptophan↗
PubMed1981

Central action of pirenzepine.

Pirenzepine, (5,11-dihydro-11-[(4-methylpiperazin-1-yl)-acetyl]-6H-pyrido-[2,3] [1,4]-benzodiazepin-6-one dihydrochloride), tested on rats and mice, did not demonstrate any conspicuous behavioral action: it did not counteract reserpine hypothermia in mice, the L-DOPA hypermotility of mice, and (with the exception of very large doses) the amphetamine hypermotility in mice and rats. The drug neither prolonged the time of immobility of rats in the behavioral despair test, nor affected the central serotonin system in rats in tests for 5-hydroxytryptophan-induced head twitches, tryptamine-induced convulsions and fenfluramine-induced hyperthermia at high ambient temperature. Pirenzepine did not affect either the hind limb flexor reflex in the spinal rat, nor the action of serotoninomimetics of it. The investigated compound had strong peripheral cholinolytic action as it inhibited salivation and lacrimation in the oxotremorine test. The oxotremorine tremor was weakened only by very high doses of pirenzepine. LD50 of the drug in mice was 412 mg/kg ip.

Animals↗
PubMed1981

Central action of ketotifen.

Ketotifen (4-/1-methyl-4-piperidylidene/-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one hydrogen fumarate) inhibited spontaneous locomotor activity and amphetamine hypermotility in mice and rats, as well as L-DOPA-induced motor stimulation in mice. It produced in mice a slight hypothermia and did not prevent reserpine-induced hypothermia; thus, it does not posses properties or tricyclic antidepressants. Ketotifen showed some features of serotoninolytic: it inhibited the head twitch response to 5-hydroxytryptophan in mice, depressed tryptamine-induced clonic convulsions in rats, antagonized fenfluramine-induced hyperthermia in rats at high ambient temperature and showed weak antiserotonin action in the flexor reflex preparation. Ketotifen did not affect spiperone- or reserpine-induced catalepsy and showed no cholinolytic activity. LD50 of ketotifen (after 24 h) was 122.5 mg/kg ip in mice and 62.6 mg/kg ip in rats.

Amphetamine↗
PubMed1981

Influence of proadifen, an inhibitor of the metabolism of drugs, on the action of imipramine and desipramine in rats.

The influence of proadifen (SKF-525-A), an agent inhibiting the metabolism of drugs, on the antidepressant action of imipramine (IMI) and desipramine (DMI) in rats was investigated. Proadifen antagonized the action of IMI when investigated in reserpine hypothermia and ptosis and in the behavioral despair test. The action of DMI in the same tests was not changed by proadifen. Proadifen lowered the level of DMI and increased the level of IMI in rat brains. The results permit to draw the conclusion that DMI plays an essential role in the action arising from IMI administration, that is, the noradrenergic--and not the serotonergic--mechanism is of essential importance.

Animals↗
PubMedDate not supplied

Antidepressant activity of S-adenosyl-L-methionine in mice and rats.

S-Adenosyl-L-methionine (SAM), main methyl donor, was tested in mice and rats in several models which are predictive of possible antidepressant activity. In the forced swimming test in rats the effect of SAM was compared with that of the tricyclic antidepressant amitriptyline. SAM decreased dose-dependently immobility time in the forced swimming test in mice and rats, these effects being antagonized by haloperidol and prazosin (the latter only in rats). Locomotor or exploratory activity in mice and rats was not increased by SAM. D-Amphetamine-induced locomotor hyper-activity in rats was increased by repeated (14 days, twice daily) treatment with SAM. Behavioural stimulation induced by D-amphetamine or L-dopa (given with benserazide) in mice was not changed by a single dose of SAM. The drug reduced hypothermia induced by apomorphine in mice. Hypothermia induced by reserpine or clonidine in mice was not antagonized. SAM increased the amplitude of the acoustic startle reflex. The above results indicate that the psychopharmacological profile of SAM resembles that of antidepressants in only some tests. The mechanism by which SAM produces its antidepressant effect needs further investigation.

Amphetamine↗
PubMedDate not supplied

Effect of local intracerebral administration of EMD 57445, a selective sigma receptor ligand, on the locomotor activity of the rat.

EMD 57445 is a new compound which has been characterized by high affinity for sigma receptor sites. It has not been shown to bind to any other receptors, including dopamine ones. However, hitherto existing data (behavioral as well as biochemical) have suggested that this drug exhibits functional antidopaminergic activity. Therefore, in the present study, the local cerebral administration of EMD 57445 has been used in order to better elucidate the actual site of action of this compound in the central nervous system. EMD 57445 given unilaterally into the nucleus accumbens, striatum and lateral ventricle decreases the locomotor activity of the rats, the effect being the most pronounced in the case of administration into the nucleus accumbens. Moreover, unilateral intraaccumbal injection of EMD 57445 significantly diminishes apomorphine (given peripherally)-induced hyperactivity. Local administration of EMD 57445 into the prefrontal cortex of the rats also attenuated the locomotor activity but the effect was statistically significant only after bilateral administration of the compound. Additionally, the lack of influence of EMD 57445, administered po, on the dopamine D1 and D2 receptor binding in the striatal membranes was observed in these studies. However, in limbic forebrain the density of D2 receptors decreased after the higher dose of EMD 57445. In conclusion, the results obtained in this paper support the hypothesis that EMD 57445 exerts antidopaminergic activity through indirect inhibition of dopamine system.

Animals↗
PubMedDate not supplied

Pharmacological profile of milnacipran, a new antidepressant, given acutely.

Pharmacological effects of acute treatment with milnacipran (MIL), a clinically active antidepressant (a noradrenaline [NA] and 5-hydroxytryptamine [5-HT] reuptake inhibitor without any affinity for neurotransmitter receptors) were studied in mice and rats. MIL inhibited the reserpine- or apomorphine-induced hypothermia in mice and enhanced the L-5-hydroxytryptophan-induced head twitches in rats. It reduced the immobility time in Porsolt's test in mice and rats, but either did not change the locomotor activity (mice) or decreased it (rats). MIL changed neither the clonidine-induced aggressiveness in mice nor the behavioral syndrome induced by oxotremorine in rats. The obtained results indicate that MIL, given acutely, shows a pharmacological profile similar to that of tricyclic NA and 5-HT reuptake inhibitors. In contrast to the antidepressants mentioned above, MIL does not exhibit an alpha1-adrenolytic or cholinolytic activity (in vivo tests).

5-Hydroxytryptophan↗
PubMedDate not supplied

Effect of sigma ligands on the cocaine-induced convulsions in mice.

It has been hypothesized that some of negative effects exerted by cocaine are mediated via sigma (sigma) receptors. This report demonstrates the effects of selective sigma ligands, panamesine, DTG, rimcazole and SA 4503, on the cocaine-induced convulsions in mice and locomotor hyperactivity in rats. Only panamesine decreased both these effects of cocaine, whereas DTG and rimcazole increased the total time of cocaine-evoked convulsions and locomotor activity. SA 4503 slightly enhanced and prolonged cocaine-induced convulsions but it was ineffective in locomotor hyperactivity test. Moreover, the increase in cocaine-induced locomotor hyperactivity evoked by DTG was antagonized by panamesine. The obtained results indicate that panamesine, a selective sigma ligand with a preference for sigma1 receptor subtype and potential antagonistic activity, decreased the effects of cocaine. DTG and rimcazole (potential sigma1/sigma2 sites agonists) as well as SA 4503 (potential sigma1 site agonist) showed rather opposite effects. These findings support the idea that sigma2 receptor subtype is involved in psychomotor stimulant effects of cocaine while sigma1 receptor subtype participates in the cocaine-induced convulsions. In addition, sigma receptor antagonists (especially sigma1 ones) are able to antagonize toxic effects of cocaine while sigma agonists facilitate them.

Animals↗
PubMedDate not supplied

Repeated imipramine treatment enhances the 7-OH-DPAT-induced hyperactivity in rats: the role of dopamine D2 and D3 receptors.

Previous studies have shown that antidepressant drugs with different pharmacological profiles, administered repeatedly, increase the locomotor hyperactivity induced by various dopaminomimetics, among others by (+/-)7-hydroxydipropylaminotetralin (7-OH-DPAT). Since, according to a recent study, this drug shows a high affinity for not only dopamine D3 but also dopamine D2 receptors, a question arises whether dopamine D3 receptors are involved in the increase in 7-OH-DPAT-elicited locomotor hyperactivity induced by repeated treatment with antidepressant drugs. The aim of the present study was to investigate the effect of imipramine (IMI), administered repeatedly, on the hyperactivity induced by 7-OH-DPAT, a dopamine D3 receptor-preferring agonist. Male Wistar rats were treated with IMI (10 mg/kg po) either acutely (single dose) or repeatedly (twice daily for 14 days). The locomotor hyperactivity induced by 7-OH-DPAT (3 mg/kg sc) was measured in photoresistor actometers. The influence of nafadotride (0.2 and 0.4 mg/kg ip), a dopamine D3-preferring antagonist or sulpiride (10 and 25 mg/kg ip), a dopamine D2/D3 antagonist, on the 7-OH-DPAT-induced locomotor hyperactivity was studied. Nafadotride (in both doses used) or sulpiride (in the higher dose only) reduced (by about 50%) the hyperactivity induced by 7-OH-DPAT. Combined treatment with nafadotride (0.2 mg/kg) and sulpiride (25 mg/kg) completely abolished the effect of 7-OH-DPAT. IMI administered repeatedly (but not acutely) enhanced the 7-OH-DPAT-induced hyperactivity. Neither nafadotride, 0.2 mg/kg (or sulpiride, 10 mg/kg), given alone nor combined treatment with both these substances changed the hyperactivity induced by repeated treatment with IMI and 7-OH-DPAT (given 2 h after the last dose of IMI). Joint treatment with nafadotride, 0.2 mg/kg, and sulpiride, 25 mg/kg, completely abolished the enhancing effect of repeated treatment with IMI and 7-OH-DPAT. The above results indicate that both types of dopamine receptors, D3 and D2, may play a substantial role in the mechanism of the 7-OH-DPAT-induced hyperactivity, as well as in the increase evoked by repeated treatment with IMI in rats.

Animals↗
PubMedDate not supplied

Repeated treatment with SA4503, a selective sigma1 receptor agonist, up-regulates alpha-adrenergic system. a behavioral study.

The obtained results indicate that SA4503, a selective sigma1 receptor agonist, given repeatedly (but not acutely) enhanced the effects of phenylephrine, alpha1-adrenoceptor agonist, and clonidine (stimulating the postsynaptic alpha1-adrenoceptors at high dose) in behavioral models (hyperexploratory activity in rats and aggressiveness in mice, respectively).

Administration, Oral↗