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Biomedical subjects

M Wielosz

Publications and source records attributed to M Wielosz.

At least 37 records · Page 2Linked to original sources
PubMed1977

Effect of two non tricyclic antidepressant drugs on [14C]5-hydroxytryptamine uptake by rat platelets.

The uptake of 14C-5-HT by rat blood platelets was examined in vitro in experimental conditions which allowed measurement of the initial velocity and excluded other passive processes across the cell membrane. In these conditions, the effect of two non tricyclic antidepressant drugs (Lilly 110140 and trazodone) was investigated. Lilly 110140 was as active as chlorimipramine and several times more active than imipramine as an inhibitor of 14C-5-HT uptake. Like chlorimipramine, Lilly 110140 appeared to be either a non-competitive or an uncompetitive inhibitor, according to the concentration of drug used. Trazodone also inhibited 14C-5-HT uptake by platelets but to a lesser extent than chlorimipramine, imipramine or Lilly 110140. m-Chlorophenylpiperazine, a possible metabolite of trazodone, was about 3 times more potent an inhibitor than the parent molecule. Both compounds acted non-competitively. Compared with published data on the effect of Lilly 110140 and trazodone on brain 5-HT, the present results support the suggestion that rat platelets are a useful pharmacological model of serotoninergic nerve endings.

Animals↗
PubMed1977

Interference by fenfluramine with the storage of 14C-5-hydroxytryptamine in rat platelets.

(+)Fenfluramine decreases the 14C-5HT stored in rat platelets both in in vitro and in in vivo systems, indicating a release of the amine. The effect of (+) fenfluramine in vitro increases by increasing the concentration of the drug, the time of incubation with platelets and the temperature. It is not accompanied by loss of lactate dehydrogenase thus excluding an unspecific damage to the platelet membrane induced by the drug. In addition it is not inhibited either by inhibitors of the uptake of 5HT (chlorimipramine, Lilly 110140) or by inhibitors of the platelet 'release reaction' (acetylsalicylic acid) or by an excess of cold 5HT in the incubation medium. The effect of (+) fenfluramine in vivo is dose-dependent and increases gradually up at least 18 hr after i.p. drug's administration. It is significantly inhibited in rats pretreated by either chlorimipramine or Lilly 110140, but not by acetylsalicyclic acid. In analogy with the effect of (+) fenfluramine on rat brain 5HT, it is suggested that this drug could enter platelets by utilizing the 5HT uptake mechanism, at least in vivo.

Animals↗
PubMed1976

Uptake of 14C-5-hydroxytryptamine by human and rat platelets and its pharmacological inhibition. A comparative kinetic analysis.

In order to approach the uptake of 14C-5HT by platelets as a first-order process, experimental conditions were selected in which accumulation of the amine either by diffusion or by other passive nonsaturable processes could be excluded. These conditions included an incubation period of 14C-5HT with human or rat platelets of 4 min or 30 s, respectively and the use of substrate concentrations around the calculated apparent Km values (0.25 - 2.0 muM). While the apparent Km values were rather similar for human and rat platelets, Vmax was about 5 times higher in rat than in human platelets. The kinetic model adopted in this study was used to evaluate the relative potency and the type of inhibiton of 14C-5HT uptake exhibited by imipramine, chlorimipramine and (+)-fenfluramine. All 3 compounds inhibited 14C-5HT uptake by platelets. Chlorimipramine was about 10 times more effective than imipramine both in rat and in human platelets. Both drugs were more potent inhibitors on human than on rat platelets. (+)-Fenfluramine was almost as active as imipramine on rat but 30 times less potent than imipramine on human platelets. Both imipramine and chlorimipramine inhibited 14C-5HT uptake by an apparent non-competitive mechanism, whereas (+)-fenfluramine appeared to act as a competitive inhibitor. No differences were found in this respect between human and rat platelets. Pharmacological or therapeutic doses of these drugs usually result in plasma concentrations similar to those found in this study to effectively inhibit platelet 14C-5HT uptake.

Adult↗
PubMed1976

The effect of lithium chloride on the activity of some psychotropic drugs.

LiCl administered for 4 days enhances amphetamine-induced locomotor stimulation, increases amphetamine toxicity in aggregated mice but does not affect amphetamine stereotypy. Administered together with nialamide, LiCl increase locomotor activity of mice and rats. The administration of this compound together with reserpine reverses central effects of its action (hypothermia, decreased motility, enhancement of hexobarbital activity).

Amphetamines↗
PubMed1975

Central action of drugs acting on the cholinergic muscarinic receptor I. Influence of cholinomimetic drugs administered into the lateral cerebral ventricle on behavior in rats.

Carbachol (CCh), physostigmine (Pht) and pilocarpine (Pil) injected into the lateral cerebral ventricle (ivtr), diminished spontaneous motility and open-field performance, lowered body temperature, depressed amphetamine-induced hypermotility, and inhibited amphetamine stereotypy. On the other hand, they had no effect on duration of hexobarbital anesthesia, except Pil, which slightly prolonged it, or on the action of threshold dose of pentetrazole and maximal electroshock. The compounds raised levels of "free" and "total" ACh, but not those of "bound" ACh. Level of NA in the brain was decreased, while level of DA was unaltered. These results are further evidence of an inhibitory influence of cholinomimetic drugs on behavior in animals.

Acetylcholine↗
PubMed1975

Central action of drugs acting on the cholinergic muscarinic receptor. II. Influence of ecothiopate administered into the lateral cerebral ventricle on behavior in rats.

Ecothiopate (Etp), 10 mug injected into the lateral cerebral ventricle (ivtr), diminished spontaneous motility and open-field performance, lowered body temperature, inhibited amphetamine-induced hypermotility and stereotypy, prolonged hexobarbital anesthesia and did not induce catalepsy. These behavioral symptoms were accompanied by lowered level of NA and elevated levels of 5-HT and 5-HIAA in the brain. No change in levels of DA were noted. Smaller doses (0-1 and 1 mug) had virtually no influence on behavior of the animals. The dose of 1 mug caused a rise in levels of 5-HIAA in the brain, but had no influence on levels of NA, DA and 5-HT.

Amphetamine↗
PubMed1975

The influence of alkaline elements on the metabolism of 5-hydroxytryptamine in rat's brain.

A single or four time-administration of Li, Na, K, Rb and Cs chlorides at the doses of 2-5 and 5 mEq/kg ip does not significantly affect 5-HT level. The level of 5-hydroxyindoleacetic acid (5-HIAA) increase only after the administration of LiCl. This increase occurs already after 1 hr and persists up to 24 hrs after the last injection. LiCl given together with probenecid induces the increase in 5-HIAA level greater than that after probenecid alone. The decrease in 5-HIAA level after pargyline-induced inhibition in MAO is more rapid in animals submitted to two action of Li. The increase 5-HIAA level in rat's brain results from Li ions-increased 5-HT turnover.

Animals↗
PubMedDate not supplied

Influence of chronic treatment with H1 receptor antagonists on the anticonvulsant activity of antiepileptic drugs.

The aim of this study was to evaluate the effects of chronic astemizole and ketotifen administration on the anticonvulsant activity of antiepileptic drugs against maximal electroshock-induced convulsions in mice. Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Brain and plasma levels of antiepileptics were measured by immunofluorescence. Astemizole (2 mg/kg) and ketotifen (8 mg/kg) significantly diminished the electroconvulsive threshold, being without effect upon this parameter at lower doses. Astemizole significantly reduced the anticonvulsant action of phenobarbital and diphenylhydantoin, but it did not affect that of carbamazepine and valproate. Moreover, ketotifen (at the subprotective dose of 4 mg/kg) remained without effect upon the protective activity of valproate, diphenylhydantoin or phenobarbital, but significantly diminished the anticonvulsant effect of carbamazepine. Histamine receptor antagonists combined with antiepileptic drugs, did not alter their brain and free plasma levels. Also, they did not influence adverse potential of carbamazepine, diphenylhydantoin and valproate while that of phenobarbital was significantly enhanced. Valproate, phenobarbital and diphenylhydantoin alone at their ED50s against maximal electroshock or combined with the histamine receptor antagonists disturbed long-term memory. The results of this study indicate that H1 receptor antagonists, should be used with caution in epileptic patients.

Animals↗
PubMedDate not supplied

Clinical and pharmacological approach to the diagnosis of paranoid schizophrenia.

The aim of the study was finding out the correlations between some clinical and biological variables in paranoid schizophrenia. The group of 16 patients with paranoid schizophrenia, chosen in careful diagnostic procedure was treated with perazine during 4 weeks time. Before and during the treatment, the following parameters: psychopathology, serum perazine and prolactin concentration, dopamine-beta-hydroxylase activity and simple reaction time were measured. We found changes of those parameters caused by the treatment. The simple reaction time retardation was side-dependent before the treatment and not side-dependent after the treatment.

Adult↗