Search PubMed⌕ Search

Biomedical subjects

C de Montigny

Publications and source records attributed to C de Montigny.

141 records · Page 8Linked to original sources
PubMed1980

Effect of chronic tricylic antidepressant treatment on the serotoninergic autoreceptor: a microiontophoretic study in the rat.

Chronic treatment with tricyclic antidepressant (TCA) drugs has been shown to enhance the responsiveness of rat forebrain neurons to serotonin (5-HT). In the present study, imipramine (5 mg and 10 mg/kg), iprindole (2.5 mg/kg), desipramine and femoxetine (5 mg/kg) were administered daily for 14 days. The response of dorsal raphe neurons to intravenous injection of LSD (4 microgram/kg) and to microiontophoretic applications of 5-HT and LSD was assessed 24 h after the last dose. The responsiveness to intravenous LSD and the effectiveness of microiontophoretic applications of 5-HT and LSD were not altered by TCA drug pretreatments. Furthermore, the treatments did not change the mean firing rate of these 5-HT neurons. Those results suggest that chronic treatment with TCA drugs does not alter the sensitivity of the 5-HT autoreceptor. Thus, the effect of the previously reported increase of postsynaptic neuron responsiveness to 5-HT would not be dampened by a decreased activity of the presynaptic neurons.

Animals↗
PubMed1979

Denervation supersensitivity to serotonin in rat forebrain: single cell studies.

To investigate the development of denervation supersensitivity to serotonin (5-hydroxytryptamine, 5-HT) in the amygdala (AMYG) and the ventral lateral geniculate nucleus (vLGN), single cell recordings, microiontophoretic, histochemical and biochemical techniques were used in the present study. 5-HT projections to the vLGN and the AMYG were destroyed by 5,7-dihydroxytryptamine (5,7-DHT, a relatively selective toxin for 5-HT neurons) injected directly into the lateral ventricle or the ascending 5-HT pathway in the ventromedial tegmentum area. Enhanced responsiveness of cells to the inhibitory effect of microiontophoretically applied 5-HT (ionto-5-HT) began to develop within 24 h and approached a maximum 7 days after 5,7-DHT pretreatment. In general, the time courses for the reduction in both the density of 5-HT fluorescent varicosities and synaptosomal 5-HT uptake activity paralleled the time course for the development of denervation supersensitivity to 5-HT. During the first 2 days after 5,7-DHT, the enhanced sensitivity was selective for 5-HT; responses to D-lysergic acid diethylamide (LSD), norepinephrine (NE) and gamma-aminobutyric acid (GABA) were unchanged. Seven or more days after 5,7-DHT there was a marked increase of the responsiveness of neurons in the vLGN and the AMYG to both 5-HT and LSD (a 5-HT agonist which is not a substrate for the high affinity 5-HT uptake system). At these later times, the responsiveness of cells in the AMYG to NE and to a lesser extent GABA was also increased. In contrast to the marked supersensitivity seen after 5,7-DHT induced denervation, chronic administration of parachlorophenylalanine, a 5-HT synthesis inhibitor, failed to induce 5-HT supersensitivity.

5,7-Dihydroxytryptamine↗
PubMed1979

Ineffectiveness of deanol in tardive dyskinesia: a placebo controlled study.

In a double-blind placebo-controlled study, deanol acetamidobenzoate, administered in doses up to 1.5 g q.d. for three weeks to chronic schizophrenic patients presenting moderate to severe tardive dyskinesia, failed to alleviate the dyskinetic movements. However, there was a tendency for a significant increase in the schizophrenic symptoms of the deanol-treated group relative to the control group. The ineffectiveness of deanol in alleviating tardive dyskinesia is consistent with its inability to enhance brain acetylcholine synthesis. The worsening of the schizophrenic symptoms may possibly result from an interference by deanol with central cholinergic function.

Adult↗
PubMed1978

Tricyclic antidepressants: long-term treatment increases responsivity of rat forebrain neurons to serotonin.

Long-term treatment of rats with clinically effective tricyclic antidepressant drugs induced a selective increase in the inhibitory response of forebrain neurons to serotonin applied by microiontophoresis. Long-term administration of some related drugs which lack antidepressant efficacy failed to induce such a change. The enhanced response to serotonin induced by the clinically active tricyclic drugs took 1 to 2 weeks to develop, a time course which correlates with the delayed onset of therapeutic effects in humans.

Action Potentials↗
PubMedDate not supplied

Quantitation of iprindole in plasma by GLC.

A specific, sensitive, rapid, and reproducible method for iprindole in human plasma was developed using gas chromatography with trimipramine as internal standard. The sensitivity of the method is of 5 ng ml-1 and a linearity was obtained for concentrations ranging from 12.5 ng ml-1 to 100 ng ml-1 with a regression coefficient of 0.9872. The plasma levels of iprindole were determined in five healthy volunteers following the administration of a single oral dose of 60 mg and in four patients admitted for endogenous depression after a 3-week administration of 90 mg d-1. Following a single oral dose to healthy volunteers, the maximum concentrations occurred between 2 and 4 h after administration of the drug and the mean half-life value was 52.5 h. In patients the steady-state concentrations of iprindole ranged between 18 and 77 ng ml-1.

Chromatography, Gas↗
PubMedDate not supplied

Placebo-controlled comparative study of the anxiolytic activity and of the pharmacokinetics of oral and sublingual lorazepam in generalized anxiety.

In a randomized crossover study, twelve patients presenting a generalized anxiety disorder received either a 1 mg oral tablet or a 1 mg sublingual tablet of lorazepam three times daily for 7 days. After a 7-day washout period, each patient received a 7-day treatment with the other tablet form. Treatments were administered in a double-blind manner using placebos of both the oral and sublingual tablets. Psychiatric evaluations were carried out before and following each of the three periods. Blood samples were drawn at intervals for 48 h following the last dose of each treatment. The plasma concentrations of lorazepam were measured by gas chromatography using an electron-capture detector. Both the oral and sublingual lorazepam produced a significant anxiolytic effect; there was no statistically significant difference between the therapeutic effectiveness of the two forms of lorazepam. The main pharmacokinetic parameters for the oral and sublingual tablets were, respectively: elimination half-life 15.6h and 11.7h; maximal concentration 40.8 ng ml-1 and 42.2 ng ml-1; time to reach maximal concentration 1.2h and 1.4h; corrected area under the curve 310.6 ng hml-1 and 313.6 ng hml-1. There was no statistically significant difference between the oral and sublingual tablets for any of the pharmacokinetic parameters measured.

Administration, Oral↗
PubMedDate not supplied

Benzodiazepines antagonize cholecystokinin-induced activation of rat hippocampal neurones.

Cholecystokinin (CCK) is a neuropeptide present in the mammalian central nervous system (CNS). In all species studied so far, the highest concentrations of this neuropeptide have been found in the cerebral cortex, the amygdala and the hippocampus. Five molecular forms of CCK having 39, 33, 13, 8 and 4 amino acid residues have been identified in the CNS, the sulphated octapeptide (CCK8) being the most abundant form detected. Specific CCK binding sites have been demonstrated in the rat, guinea pig and human brain. CCK8, applied by microiontophoresis to deep cortical neurones and hippocampal pyramidal neurones, has a powerful excitatory effect, whereas the non-sulphated CCK octapeptide has no such effect on these neurones. Low doses of benzodiazepines depress the spontaneous activity of hippocampal pyramidal neurones. We report here that benzodiazepines at very low doses antagonize selectively the CCK8-induced activation of rat hippocampal pyramidal neurones. This antagonistic action might be involved in the anxiolytic effect of these drugs.

Action Potentials↗
PubMedDate not supplied

Pharmacokinetic study of zimelidine using a new GLC method.

A specific, sensitive, rapid and reproducible analytical method for zimelidine [3-(4-bromophenyl)-N,N-dimethyl-3(3-pyridyl)allylamine] and its biologically active demethylated metabolite, norzimelidine, in human plasma was developed using gas-liquid chromatography (GLC) with loxapine as the internal standard. A good separation of zimelidine and norzimelidine was obtained following derivatisation of norzimelidine with heptafluorobutyric anhydride, the retention times being 6.16 and 10.35 minutes, respectively. The sensitivity of the method is 5 ng/ml for zimelidine and norzimelidine. Plasma concentrations of zimelidine and norzimelidine were determined in 10 healthy volunteers following the administration of a single oral dose of 100mg zimelidine. Zimelidine was rapidly absorbed, giving a mean peak plasma concentration of 103.9 +/- 34.8 ng/ml. The mean plasma elimination half-life was 8.4 +/- 2.0 hours for zimelidine and 19.4 +/- 3.6 hours for norzimelidine. After long term administration of zimelidine (100mg bid for the first week, 100mg tid for the second week and 100mg am and 200mg pm for the third and fourth weeks) to 2 depressed patients, plasma concentrations of norzimelidine were 2 to 4 times higher than those of zimelidine.

Adult↗