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Biomedical subjects

G Skuza

Publications and source records attributed to G Skuza.

At least 37 records · Page 2Linked to original sources
PubMed1994

Memantine, amantadine, and L-deprenyl potentiate the action of L-dopa in monoamine-depleted rats.

Some treatments used for Parkinson's disease attenuate locomotor depression in rats treated with reserpine and alpha-methyl-p-tyrosine. In the present study memantine (2.5, 5.0 mg/kg), amantadine (10, 20 mg/kg) (both uncompetitive NMDA antagonists), and L-deprenyl (1.0, 5.0 mg/kg; MAO-B inhibitor) were tested for possible synergistic interactions with the dopamine agonists: bromocriptine (2.5, 5.0 mg/kg) and L-dopa (50, 100 mg/kg, +benserazide, 100 mg/kg). At higher doses, memantine (10 mg/kg), amantadine (40 mg/kg), bromocriptine (5 and 10 mg/kg) and L-dopa (100, 200 mg/kg) but not L-deprenyl (up to 10 mg/kg) produced a pronounced increase in locomotor activity when given alone. The combination of memantine, amantadine and L-deprenyl with bromocriptine did not result in synergism of action and, at best, an additive effect was seen. On the other hand the combination of these agents with L-dopa produced a pronounced synergistic effect. Hence, the clinical observation that coadministration of L-dopa with either memantine or amantadine results in enhancement of their action is also reflected in an animal model of Parkinson's disease. Such a combination therapy should allow the use of lower doses of both drugs which may reduce the occurrence of side effects and may also be predicted to have additional benefits related to the neuroprotective properties of memantine, amantadine, and L-deprenyl.

Amantadine↗
PubMed1994

Pharmacological action of zotepine and other antipsychotics on central 5-hydroxytryptamine receptor subtypes.

The effect of the atypical neuroleptic zotepine (CAS 26615-21-4), in comparison with clozapine, risperidone and haloperidol, on the responsiveness of different 5-hydroxytryptamine (5-HT1) receptor subtypes to their agonists was examined in rats and mice. The above antipsychotics were investigated in the following behavioural tests: 8-OH-DPAT (8-hydroxy-dipropylaminotetralin)-induced behavioural syndrome in rats, mCPP (mchlorophenylpiperazine)-induced hypothermia in mice and mCPP-induced hypoactivity measured in the open field in rats. Zotepine, clozapine and haloperidol did not affect the behavioural syndrome induced by 8-OH-DPAT (the selective agonist of 5-HT1A, receptor), only risperidone (used in higher doses) attenuated the effect of 8-OH-DPAT. The mCPP-induced hypothermia in mice (a 5-HT1B effect) was affected by neither zotepine nor clozapine, risperidone and haloperidol, all of them used in low doses which did not influence per se the body temperature of mice. All the tested antipsychotics given at high doses induced hypothermia in control mice; at the same time, zotepine, clozapine and risperidone attenuated the hypothermic effect of mCPP. mCPP decreases the exploratory activity of rats, this effect being considered to be mediated by 5-HT1C receptors. The tested antipsychotics, used in low doses, influenced neither the exploratory activity nor the hypoactivity induced by mCPP. When used at higher doses, they induced hypoactivity in control rats; the hypoactivity after joint administration of zotepine, risperidone or haloperidol and mCPP was significantly greater than after mCPP alone, whereas clozapine slightly attenuated the effect of mCPP.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Some central effects of CGP 37849 and CGP 39551, the competitive NMDA receptor antagonists: potential antiparkinsonian activity.

Two new competitive NMDA receptor antagonists with oral activity CGP 37849 (D,L-E-amino-methyl-phosphono-3-pentenoic acid) and its ethyl ester CGP 39551 were studied in rats. CGP 37849 did not change the locomotor activity or increased it. The hyperactivity induced by CGP 37849 was antagonized by haloperidol but not idazoxan or prazosin. CGP 39551 decreased the locomotor activity. The studied compounds did not increase the locomotion in monoamine-depleted (pretreated with reserpine and alpha-methyl-p-tyrosine) rats. Clonidine induced antiakinetic effect in monoamine-depleted rats. This effect was more pronounced after joint administration of clonidine and CGP 37849 or CGP 39551. The locomotor hyperactivity induced by joint administration of CGP 37849 and clonidine was inhibited by haloperidol but not prazosin or idazoxan. CGP 37849 but not CGP 39551 also enhanced antiakinetic effect of L-DOPA (given together with benserazide) in monoamine-depleted rats. CGP 37849 antagonized the spiperone- and fluphenazine-induced catalepsy; CGP 39551 had considerably weaker antagonistic effect. The reserpine-induced catalepsy was attenuated by CGP 37849. MK-801, a non-competitive NMDA antagonist inhibited spiperone- but not reserpine-induced catalepsy. The obtained results indicate that CGP 37849 administered alone or in combination with L-DOPA or clonidine may be a potential antiparkinsonian drug.

2-Amino-5-phosphonovalerate↗
PubMed1992

The effect of antidepressant drugs on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist.

It was found earlier that imipramine, amitriptyline and citalopram enhanced the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist, in rats. Now, three other antidepressants: (+)-oxaprotiline, an inhibitor of the uptake of noradrenaline, (-)-oxaprotiline, an enantiomer devoid of any effect on the uptake of noradrenaline and fluoxetine, an inhibitor of the uptake of 5-hydroxytryptamine, have been examined in male Wistar rats. All those antidepressants, given in a single dose, increased the MK-801-induced locomotor hyperactivity. That increase was completely antagonized by haloperidol and partly by SCH 23390 and (+/-)-sulpiride; prazosin was inactive. Repeated administration of antidepressants produced a similar but more potent (than acute one) enhancement of the action of MK-801. Also, in that case haloperidol and SCH 23390 produced the strongest antagonistic effect; (+/-)-sulpiride and prazosin had a distinctly less potent action. Another effect of MK-801, anticonvulsant activity (electroshock-induced convulsions), was not increased by the antidepressants studied. These results indicate that antidepressants with a different pharmacological profile, increased the MK-801-induced locomotor hyperactivity, this effect being probably indirectly mediated, at least in part, by a dopamine mechanism.

Animals↗
PubMed1992

Effects of MK-801 and antidepressant drugs in the forced swimming test in rats.

The effects of MK-801, a non-competitive NMDA receptor antagonist, and of antidepressant drugs were studied in the forced swimming test in rats. MK-801 reduced immobility time. Combined treatment with MK-801 + imipramine induced a stronger effect in Porsolt's test than administration of either drug alone. Citalopram was inactive when given alone but it potentiated the antidepressant-like effect of MK-801. Haloperidol and prazosin antagonized the effect induced by MK-801 + IMI or CIT. Mianserin interacted with MK-801 in a similar way but to a lesser extent. Its effect was antagonized by haloperidol but not by prazosin. The reduction of the immobility time was also observed in those experimental paradigms in which the locomotor activity was not increased. The results indicate that synergism may exist between antidepressants and MK-801.

Animals↗
PubMed1991

Antidepressant drugs increase the locomotor hyperactivity induced by MK-801 in rats.

MK-801, a non-competitive NMDA receptor antagonist, induced the locomotor hyperactivity in rats. Imipramine (IMI), amitriptyline (AMI), citalopram (CIT) given acutely increased the MK-801-induced locomotor hyperactivity. Mianserin (MIA) showed a similar but weaker effect. Haloperidol completely blocked the hyperactivity induced by the antidepressant drug (AD) + MK-801. Prazosin had an only weak antagonistic effect. Repeated treatment with AD increased the MK-801 locomotor hyperactivity to a greater extent than acute treatment. This effect was completely blocked by haloperidol and only partly by prazosin. The obtained results indicate that the dopamine system may be involved, at least in part, in the potentiating effect of the combined treatment with AD + MK-801.

Amitriptyline↗
PubMed1991

The effect of (+)- and (-)-oxaprotiline administered repeatedly on the dopamine system.

The behavioural and biochemical effects of repeated (14 and 28 days) treatment with (+)-oxaprotiline (a noradrenaline uptake inhibitor) and (-)-oxaprotiline (levoprotiline, without influence on noradrenaline uptake; the clinically active antidepressant) were studied in rats. Both those enantiomers given repeatedly increased the locomotor and exploratory activity and reduced the immobility time in Porsolt's test. The D-amphetamine-induced locomotor hyperactivity, as well as the stereotypies induced by D-amphetamine and apomorphine, were increased by the oxaprotilines. Single-dose treatment with both the oxaprotilines was not effective in the tests mentioned above. Repeated (+)-oxaprotiline administration reduced the binding (Bmax but not KD) to dopamine D-1 receptors in the striatum and limbic system; levoprotiline was inactive. The binding to dopamine D-2 receptors was not changed by either drug. Both the enantiomers showed only low affinity for brain dopamine D-1 and D-2 receptors in vitro. The obtained results indicate that chronic treatment with (+)- and (-)-oxaprotiline increases behavioural responsiveness of the dopamine mesolimbic and striatal systems.

Animals↗
PubMed1990

Some central pharmacological effects of (+)- and (-)-oxaprotiline.

The central action of oxaprotiline (OXA) enantiomers, administered in a single dose, was studied in rats and mice. (+)-OXA and (-)-OXA attenuated reserpine- and apomorphine-induced hypothermia [(+)-OXA in a more potent manner] in mice and reduced the immobility time in the behavioural despair test in rats. Both OXA enantiomers inhibited locomotor activity in mice and rats, and enhanced and prolonged amphetamine- and apomorphine-induced stereotypy in rats. (-)-OXA potentiated the amphetamine hyperactivity in rats, but not in mice. Nomifensine hyperactivity in rats was unaffected by either enantiomer, and locomotor hypoactivity induced by low doses of apomorphine was also unchanged, as was L-DOPA-induced locomotor hyperactivity in mice. Apomorphine-induced climbing in mice was attenuated by (+)-OXA. Clonidine locomotor hypoactivity and hypothermia were unchanged, and clonidine-induced aggressiveness was attenuated by (+)-OXA. Neither OXA enantiomer affected the action of oxotremorine. In some tests the effect of OXA was stronger at 3 h than at 1 h after administration. The above results indicate that both OXA enantiomers--in particular (-)-OXA--increase some dopaminergic behavioural effects in rats.

Animals↗
PubMed1990

Behavioural and neurochemical effects of Ro 40-7592, a new COMT inhibitor with a potential therapeutic activity in Parkinson's disease.

Behavioural and some neurochemical effects of Ro 40-7592 (3,4-dihydroxy-4'-methyl-5-nitrobenzophenone), a new COMT inhibitor, were studied in rats and mice. Ro 40-7592 increased the effect of L-DOPA (plus benserazide) on locomotor activity, reserpine-induced hypothermia, and catalepsy induced by pimozide, haloperidol and fluphenazine. Locomotor hyperactivity induced by amphetamine or nomifensine, as well as stereotypy induced by amphetamine (but not apomorphine), were also increased by Ro 40-7592. The drug stimulated exploratory activity in the open field test. It decreased the levels of HVA and 3-MT, increased the level of DOPAC but did not change the levels of dopamine in the striatum, nucleus accumbens and frontal cortex. These results indicate that Ro 40-7592 may improve the therapy with L-DOPA (plus decarboxylase inhibitor) of Parkinson's disease.

Animals↗
PubMed1989

The influence of repeated treatment with imipramine, (+)- and (-)-oxaprotiline on behavioural effects of dopamine D-1 and D-2 agonists.

The paper examined the action of imipramine, (+)- and (-)-oxaprotiline, administered repeatedly to rats, on the behavioural effects of the dopamine D-1 and D-2 agonists, SKF 38393 and quinpirole, respectively. The three antidepressants studied, given in the single dose or repeatedly, attenuate the enhanced grooming evoked by SKF 38393. The locomotor hyperactivity, evoked by quinpirole administered s.c., is increased by repeated but not single-dose treatment with imipramine and (+)-oxaprotiline [but not with (-)-oxaprotiline]. Quinpirole at a low dose produces the locomotor hypoactivity which is attenuated by repeated, but not single-dose, treatment with the anti-depressants studied here. Repeated imipramine and (+)-oxaprotiline [but not (-)-oxaprotiline] increase the locomotor activity effect of quinpirole injected into the nucleus accumbens. The results indicate that the enhanced responsiveness of the dopamine system, observed previously after repeated treatment with antidepressants, may be mediated by the dopamine D-2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Antidepressants given repeatedly increase the behavioural effect of dopamine D-2 agonist.

The effects of single or repeated doses of antidepressant drugs (imipramine, amitriptyline, citalopram, mianserin) on rat locomotor hyperactivity induced by quinpirole, a dopamine D-2 receptor agonist, was investigated. Single doses of antidepressants do not change the effect of quinpirole, but enhance it when they are administered repeatedly. This enhancement is inhibited by (+/-)-sulpiride, a dopamine D-2 receptor antagonist. The results obtained indicate that the enhancement of dopaminergically-stimulated hyperactivity induced by repeated doses of antidepressants is mediated by dopamine D-2 receptors.

Amitriptyline↗
PubMed1987

Pharmacological properties of EXP 561, a potential antidepressant drug.

The compound EXP 561 (1-amino-4-phenylbicyclo-[2,2,2]-octane), an inhibitor of the noradrenaline (NA), 5-hydroxytryptamine (5-HT) and dopamine (DA) uptake, a potential antidepressant agent, was studied in tests for evaluation of antidepressant drugs (AD). In most experiments (the apomorphine and reserpine hypothermia, the behavioural despair test, the blood pressure increases induced by NA and 5-HT) EXP 561 revealed similar activities as tricyclic AD. EXP 561 evoked stimulation of the hind limb flexor reflex in spinal rats, blocked by prazosin, metergoline and clomipramine. EXP 561 administered repeatedly in mice (twice daily for 14 days) did not evoke the adaptive changes induced by AD inhibiting the amine uptake, i.e. it did not enhance the amphetamine locomotor hyperactivity, did not potentiate the clonidine aggressiveness (at a lower dose, while at a higher one it acted less potently than when given acutely) or did not change the reserpine effect on the locomotor activity. EXP 561 showed a poor affinity to alpha 1-adrenoceptor (IC50 was 135,000 nM). The results indicate that the inability to induce adaptive changes is a feature which differentiates EXP 561 from tricyclic AD.

Aggression↗
PubMed1986

Central action of the antidepressant drug pirlindole.

The central action of 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole hydrochloride (pirlindole, PIR) in mice and rats was studied. PIR inhibited the 3H-5-hydroxytryptamine (5-HT) uptake in the rat cerebral cortex, not affecting the uptake of 3H-noradrenaline. PIR counteracted the reserpine ptosis but did not alter the apomorphine hypothermia. It enhanced the L-dopa effect on the locomotor activity and the L-5-hydroxytryptophan (L-5-HTP)-induced head twitch reaction in mice. PIR also facilitated the effect of L-dopa and L-5-HTP on the hind limb flexor reflex of the spinal rat. The clonidine sedation (but not hypothermia) was attenuated by PIR. PIR given repeatedly for 18 days increased the binding of 3H-prazosin in the brain cortex (decreasing the KD value), but did not affect the binding of 3H-dihydroalprenolol. The obtained results indicate that PIR inhibits the 5-HT uptake, displays characteristics of a monoamineoxidase inhibitor and, when given repeatedly, increases the binding to alpha 1-adrenoceptors in the cerebral cortex.

5-Hydroxytryptophan↗
PubMed1984

Repeated treatment with antidepressant drugs increases the behavioural response to apomorphine.

The effect of repeated treatment (twice a day for 14 days) with antidepressant drugs (AD): imipramine, amitriptyline, zimelidine, citalopram and mianserin on the behavioural response to apomorphine in rats (open field test) was investigated. AD studied, given alone in a single dose or repeatedly, do not change the rats behaviour. A repeated but not single-dose treatment with AD facilitates the behaviour stimulation induced by apomorphine. This facilitation is observed 2 hours after the last dose of imipramine, zimelidine, citalopram and mianserin but 72 hours after the last dose of amitriptyline. The results presented suggest that the AD given repeatedly are able to increase the responsiveness of the brain DA system, probably the mesolimbic one.

Amitriptyline↗
PubMed1983

Reserpine-induced locomotor stimulation in mice chronically treated with typical and atypical antidepressants.

Previous studies have shown that chronic treatment with antidepressants (AD) leads to an increased responsiveness of NA systems to noradrenaline (NA) or its agonist. In the present paper the influence is described of a prolonged treatment with AD of different pharmacological profiles on the effect of reserpine in the first phase of its action (amine release). It has been found that in mice treated chronically (14 days, twice a day, i.p.) with imipramine, amitriptyline, maprotiline, (+)-oxaprotiline, zimelidine, citalopram, mianserin and iprindole, the injection of reserpine induces stimulation of the locomotor activity. Only (-)-oxaprotiline and fluvoxamine do not evoke this effect. AD given alone (both single and repeated doses), reserpine alone, AD in a single dose administered jointly with reserpine do not induce the locomotor stimulation. These results suggest that a prolonged treatment with AD increases the responsiveness of the dopamine (DA) mesolimbic system and/or the NA system.

Animals↗