Biomedical subjects

G Skuza

Publications and source records attributed to G Skuza.

77 records · Page 5Linked to original sources

PubMedDate not supplied

Some behavioral effects of 1,3-di-o-tolylguanidine, opipramol and sertraline, the sigma site ligands.

1,3-Di-o-tolylguanidine (DTG), opipramol (OPI) and sertraline (SER), sigma site ligands, were studied in Wistar rats and Albino Swiss mice, mainly with regard to their interaction with dopamine drugs. DTG and SER (at the highest doses only) decreased the spontaneous locomotor activity. DTG did not change the amphetamine locomotor hyperactivity, while OPI and SER decreased it. The amphetamine stereotypy was slightly increased (prolonged) by all the three drugs. OPI antagonized the locomotor hyperactivity, stereotypy, aggression and climbing, all those being induced by apomorphine; DTG inhibited only the aggression, while SER-the aggression and climbing (the latter was also inhibited by paroxetine, which showed no affinity for sigma sites). DTG and SER (but not paroxetine) were able to increase the locomotor hyperactivity induced by quinpirole. That effect was antagonized by OPI which-when given alone-did not affect the quinpirole hyperlocomotion. The reserpine-induced akinesia was not affected by DTG, OPI or SER; the L-DOPA hyperactivity in reserpinized rats was changed (increased) by DTG only. DTG and SER (also paroxetine and citalopram), but not OPI, increased the cocaine locomotor hyperactivity. All the three sigma ligands given alone did not evoke catalepsy; the haloperidol- and spiperone-induced catalepsy was attenuated by DTG and OPI, but increased by SER. The MK-801-induced hyperactivity was decreased by DTG, but increased by OPI and SER. In the forced swimming test, only DTG slightly reduced the immobility time; the reduction of the immobility time induced by MK-801 was not changed by DTG, but increased by OPI and SER. Only DTG evoked a dose-dependent decrease in the body temperature, which was not changed by rimcazole. The above results indicate that the sigma site ligands studied differ in their pharmacological profile; however, it is still difficult to determine unequivocally whether they show agonistic or antagonistic properties.

1-Naphthylamine↗

PubMedDate not supplied

Neuropsychopharmacological profile of remoxipride in comparison with clozapine.

Central effects of remoxipride /(-)-(S)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-6-dimethoxybenz amide hydrochloride, RPD/, one of newer antipsychotic drugs with high affinity to sigma sites was studied in comparison with clozapine (CLOZ), another atypical antipsychotic agent, devoid of such an activity. It has been found that RPD decreased the locomotor activity of naive rats, as well as hyperactivity induced by D-amphetamine and apomorphine. The drug antagonized stereotypy induced by both dopamine agonists as well as apomorphine-induced climbing in mice. RPD shortened the time of SKF 38393 (dopamine D1 receptor agonist)-induced grooming in rats. Moreover, it markedly decreased quinpirole (dopamine D2/3 receptor agonist)-induced hyperactivity of rats, and less potently inhibited stimulatory activity induced by cocaine and MK-801 (non-competitive NMDA receptor antagonist). The drug impaired retention of conditioned avoidance responses and induced catalepsy in rats, at relatively high doses though. The effects of CLOZ differed to some extent from those of RPD. The former did not antagonize the apomorphine-induced stereotypy and decreased that caused by D-amphetamine less potently than RPD did. Besides, it did not induce catalepsy, even at relatively high doses while its inhibitory activity towards apomorphine- and quinpirole-induced hyperactivity, as well as locomotor activity of naive rats were much less potent. The effects of RPD and CLOZ in other experimental models were comparable. The obtained results indicating many similarities between psychopharmacological profiles of RPD and CLOZ with some essential differences as well as an equivalence of RPD central effects and the activity of EMD 57445 (selective sigma ligand devoid of any effects at other receptors) permit a supposition that, beside dopamine receptors, the sigma receptors may also be of importance to the mechanism of action of RPD.

Animals↗

PubMedDate not supplied

Effect of 1,3-di-o-tolylguanidine (DTG), rimcazole and EMD 57445, the sigma receptor ligands, in the forced swimming test.

As it is known, sigma receptor ligands have been able to modulate the central neurotransmitter systems, including noradrenergic-, NMDA-ergic- and dopaminergic ones, which are essential for the mechanism of action of antidepressant drugs. Therefore, it can be assumed that some selective sigma ligands can possess antidepressant-like activity. In the present studies 1,3-di-o-tolylguanidine (DTG), rimcazole (RIM) and EMD 57445 were examined in the forced swimming test in rats and mice. DTG and RIM decreased the immobility time in mice. EMD 57445 was inactive but it antagonized the anti-immobility effects of DTG and RIM. Both latter drugs did not change the locomotor activity of mice, EMD 57445 at higher dose decreased it. In addition, DTG showed antidepressant-like activity in rats, this effect being counteracted by EMD 57445. At the same time both drugs attenuated the spontaneous motor activity in rats. Taken together, the present results suggested that DTG and RIM may possess sigma agonistic activity while EMD 57445--the antagonistic one. Further investigations are needed to support agonistic/antagonistic activities of the studied sigma ligands and to elucidate the potential involvement of sigma site subtypes in this model.

Animals↗

PubMedDate not supplied

EMD 57445, the selective sigma receptor ligand, has no effect on the 5-hydroxytryptamine system.

The behavioral and biochemical effects of EMD 57445, a selective sigma receptor ligand with potential antipsychotic activity, on the 5-hydroxytryptamine (5-HT) system were studied in rats and mice. The drug influence was investigated in three behavioral tests: 8-OH-DPAT (5-HT1A agonist)-induced behavioral syndrome in rats, m-chlorophenylpiperazine (m-CPP, 5-HT1B agonist)-induced hypothermia in mice and L-5-hydroxytryptophan (L-5-HTP)-induced head twitches (5-HT2A stimulation) in rats. EMD 57445 did not show any activity in all three behavioral models. In biochemical studies, no changes in the 5-HT and 5-HIAA levels in rat brain cortex, nucleus accumbens, striatum, hypothalamus and hippocampus were found. The results indicate that EMD 57445 does not interact with 5-HT (5-HT1A, 5-HT1B, 5-HT2A) receptor subpopulations and does not affect 5-HT metabolism.

5-Hydroxytryptophan↗

PubMedDate not supplied

Effect of EMD 57445, the selective sigma receptor ligand, on the turnover and release of dopamine.

EMD 57445 (1, 3 and 10 mg/kg, po), a selective sigma receptor ligand without an affinity to dopamine receptors, induced potent, dose-dependent increases in the tissue DOPAC and HVA levels in the rat brain cortex, nucleus accumbens and striatum. The extracellular DOPAC and HVA levels after EMD 57445 and (3 and 10 mg/kg, po) administrations, measured by microdialysis in the rat prefrontal cortex, were also increased, without significant effects on the outflow of dopamine.

Animals↗