Search PubMed⌕ Search

Biomedical subjects

O Rascol

Publications and source records attributed to O Rascol.

At least 145 records · Page 8Linked to original sources
PubMed1990

Cardiovascular effects of central injection of acetylcholine in anaesthetized dogs: a role for vasopressin release.

1. The effect of an intracisternal injection of 20 micrograms kg-1 of acetylcholine was studied on systolic and diastolic blood pressures, heart rate, and plasma levels of noradrenaline, adrenaline, vasopressin, plasma renin activity and atrial natriuretic factor in chloralose-anaesthetized dogs, 8 of which were normal and 7 with diabetes insipidus (deprived of vasopressin secretion by surgical lesion of the hypothalamoneurohypophysial system). 2. Acetylcholine significantly increased systolic and diastolic blood pressures in both groups of animals. However, the rise in blood pressure was significantly shorter lived in the dogs with diabetes insipidus. 3. Acetylcholine significantly increased plasma levels of noradrenaline but not adrenaline in control animals and in dogs with diabetes insipidus. Noradrenaline and adrenaline responses after acetylcholine were not different in the two groups of animals. 4. Acetylcholine induced a significant increase in vasopressin plasma levels only in control animals while in dogs with diabetes insipidus vasopressin remained at nearly undetectable levels. 5. Acetylcholine significantly increased atrial natriuretic factor plasma levels only in control dogs. 6. Although plasma renin activity increased in both groups of animals after the i.c. injection of acetylcholine, this change was not significant in any group. 7. These results suggest that, in the anaesthetized dog, the central injection of acetylcholine induces a rise in blood pressure through both an increase in sympathetic outflow and a release of vasopressin.

Acetylcholine↗
PubMed1990

Blood pressure and plasma catecholamines in never-treated parkinsonian patients: effect of a selective D1 agonist (CY 208-243).

We found blood pressure (BP), heart rate (HR), plasma norepinephrine (NE), and epinephrine (E) levels in the lying and the standing positions to be similar in never-treated parkinsonian patients (stages 1 and 2) and age-matched controls. CY 208-243, a new centrally active D1 agonist, significantly decreased BP, HR, and NE (but not E) values in the lying position; it elicited orthostatic hypotension and blunted the rise in NE elicited by standing up. These results indicate that the early stages of Parkinson's disease are not accompanied by major changes in autonomic cardiovascular function and suggest the involvement of central D1-receptors in the control of sympathetic tone.

Antiparkinson Agents↗
PubMed1990

[Effect of verapamil independent of its calcium channel antagonist action on hippocampal pyramidal neurons in rats].

The effects of verapamil, the phenylalkylamine calcium channel antagonist, have been studied on rat hippocampal pyramidal neurons, using intracellular recordings in an in vitro slice preparation. At low concentrations (1-10 microM), verapamil had no effect on these neurons. At higher concentrations (100-150 microM), it induced a progressive blockade of the slow component of the after-hyperpolarizing potential (AHP), but did not affect the fast one. Verapamil also blocked the slow inhibitory postsynaptic potential (sIPSP), but not the fast one. Pharmacological responses to the application of baclofen and serotonin were abolished, while the response to GABA was not. In addition, the size of the calcium spike was increased by verapamil, while the AHP and the sIPSP were already blocked. These results suggest that verapamil, applied at high concentrations, has an inhibitory effect on potassium conductances, independent of its calcium antagonist property.

Action Potentials↗
PubMed1990

[Comparison of bromocriptine and levodopa as first line treatment of Parkinson's disease: results of a 3-year prospective randomized study].

The long term effects of a first line treatment with levodopa or bromocriptine were compared in 36 previously untreated patients with Parkinson's disease in a prospective randomized trial: 18 patients were treated with levodopa alone (mean dose: 485 +/- 71 mg daily) whereas 18 others received bromocriptine alone (mean dose: 55 +/- 6 mg daily) during 36 +/- 3 and 31 +/- 3 months respectively. We observed a similar decrease in the Columbia rating scale but the nature of long term side effects was different in the two groups: patients on levodopa developed peak-dose dyskinesias (5 cases), wearing off akinesia (1 case) and on-off effects (1 case). Under bromocriptine treatment, 2 patients developed severe psychosis whereas one suffered from primary lack of drug effectiveness and 5 others from late decrease of drug effectiveness. These results suggest the potential value of relatively high doses of D2 dopamine agonists (such as bromocriptine) in the first line treatment of Parkinson's disease: however, their use can be limited by their decrease of effectiveness after several years and/or the occurrence of severe neuropsychiatric side-effects.

Bromocriptine↗
PubMed1990

[Neuroleptic malignant-like syndrome following levodopa withdrawal].

The description of a syndrome similar to the neuroleptic malignant syndrome but occurring after levodopa withdrawal in a parkinsonian patient is reported. The imputation of levodopa withdrawal is analyzed according to the method of assessment of unexpected drug reactions used by the French centers of pharmacovigilance. This case is compared to 8 other published ones.

Aged↗
PubMed1990

CQA 206-291: a novel dopamine agonist in the treatment of Parkinson's disease.

The antiparkinsonian efficacy and tolerability of CQA 206-291, a novel ergoline derivative with potent dopamine agonist properties, were studied during 2 months of treatment in 72 parkinsonian patients. In 36 de novo patients (patients who have not previously been treated with levodopa or dopamine agonists), CQA 206-291 was studied in an open design, while in 36 levodopa-treated patients, CQA 206-291 was studied in a randomized, double-blind, parallel-group, placebo-controlled design. CQA 206-291 induced in both groups a significant antiparkinsonian effect with an effective dose range of 5-30 mg/day. The spectrum of adverse events was similar to what is commonly observed with dopamine agonists. Further studies are required to assess the putative therapeutic advantages of CQA 206-291 when compared to other antiparkinsonian drugs.

Aged↗
PubMed1989

Omega-conotoxin GVIA blocks synaptic transmission in the CA1 field of the hippocampus.

The effects of omega-conotoxin GVIA (omega-CgTx), a peptide isolated from the venom of a marine mollusc, were studied in rat hippocampal neurons. Intracellular recordings from the CA1 area were made for the purpose in in vitro slice preparations. Omega-CgTx (0.1-1 microM) rapidly and irreversibly blocked the EPSP and the IPSPs elicited by electrical stimulation of Schaffer collaterals/commissural fibers. Omega-CgTx also blocked the slow cholinergic EPSP induced by electrical stimulation of cholinergic afferents. The postsynaptic effects of baclofen or carbachol remained unchanged in the presence of omega-CgTx and other postsynaptic calcium-dependent events such as afterhyperpolarization were not affected by omega-CgTx. These results suggest a presynaptic action of omega-CgTx through the blockade of neurotransmitter release. Omega-CgTx might act in the hippocampus by blocking presynaptic N-type voltage-sensitive calcium channels.

Animals↗
PubMed1989

[Antiparkinsonian drugs].

Levodopa (+ dopa decarboxylase inhibitor) is the most active of all drugs used in the treatment of Parkinson's disease. It acts on both akinesia and rigidity and improves the prognosis of the disease by increasing life expectancy. But levodopa also produces late side-effects: it often induces abnormal movements, fluctuations in motor performance, on-off effects, psychotic hallucinations, etc. Since these late side-effects remain difficult to treat, it is always necessary to assess the benefits and risks of the first treatment with levodopa. Anticholinergic drugs, which mainly act on tremor, must be used with caution since they may induce memory alterations and often confusional states in aged parkinsonians. Dopamine agonists are prescribed as adjuvant therapy in the treatment of the late side-effects of levodopa. New drugs (selegiline), new pharmaceutical preparations (sustained release forms), the first treatment of the disease (levodopa alone versus agonists alone versus levodopa + agonists), together with the new pharmacological approaches (brain grafts, drug infusions) are now under clinical evaluation.

Antiparkinson Agents↗
PubMed1989

Rhythmical bursting activity and GABAergic mechanisms in the medial septum of normal and pertussis toxin-pretreated rats.

The possible involvement of GABA in the control of the rhythmical bursting activity (RBA) of septo-hippocampal neurons (SHNs) has been studied in the rat in vivo. The discharge frequency of SHNs was modified by the iontophoretic application of a GABA agonist and antagonist as well as by the application of the GABA uptake blocker, nipecotic acid. The GABAB agonist baclofen inhibited the SHNs' activity, this effect being antagonized by the GABAB antagonist phaclofen. However, these different pharmacological manipulations did not modify the RBA frequency. Pretreatment of the rats with pertussis toxin, a substance which is known to block the events mediated by G-proteins (Gi or Go), decreased the RBA frequency. Neither agonists nor antagonists of GABAA or GABAB types had significant effects on the rhythmical bursting activity of SHNs. The effect of pertussis toxin suggests that other neurotransmitters or intrinsic mechanisms involving a G-protein influence this rhythm.

Action Potentials↗
PubMed1989

Interferons and multiple sclerosis.

Interferons (IFNs) are a family of proteins with antiviral, antitumoral and immunomodulating properties. Multiple Sclerosis (MS) is a CNS disease in which the immune reaction (IR) is the cause of the inflammatory demyelinating lesions. IFNs have been demonstrated in active lesions. The location of IFN gamma on astrocytes suggests an enhancing activity on IR by inducing Ia antigen expression on these cells. In contrast, IFN alpha/beta located on microglial cells and astrocytes might limit the growing lesion. MS patients frequently present a defective response of NK cell activity and an abnormally low production of IFNs reflecting immune dysregulation. The therapeutic trials available to date are discussed: IFN gamma possesses a severe deleterious effect but IFN alpha/beta are still under consideration due to a possible beneficial activity.

Humans↗
PubMed1989

Abnormal ocular movements in Parkinson's disease. Evidence for involvement of dopaminergic systems.

Quantitated automated electro-oculographic data from 45 parkinsonian patients were compared with those from 30 normal control subjects. Patients were selected with idiopathic Parkinson's disease without other associated neurological disease or dementia; 20 had never received antiparkinsonian drugs and in 25 such treatment had been stopped for at least 2 days. Saccade latency, amplitude and peak velocity, smooth pursuit peak velocity, optokinetic nystagmus (OKN) maximal and mean velocities and vestibulo-ocular reflex (VOR) suppression by vision or imagination were significantly altered in patients, whereas VOR gain in darkness was normal. Alterations of saccade latency and smooth pursuit peak velocity were more severe in the more advanced stages of the disease and saccade latency directed towards the symptomatic side was slightly delayed in hemiparkinsonian patients. Saccade amplitude improved 90 min after a single oral dose of L-DOPA. These results suggest a possible dopaminergic control of some ocular movements.

Adult↗
PubMed1989

Effect of apomorphine on adrenal medullary catecholamine levels.

The effects of the dopamine receptor agonist, apomorphine, on the total catecholamine content of the adrenal medulla were studied in normotensive rats. Apomorphine (3, 15, 30 mg/kg SC) induced a dose-dependent decrease in catecholamine content of the adrenal gland. The action of apomorphine was suppressed by previous treatment with the non specific dopamine receptor antagonist, haloperidol (9 mg/kg IP), or the D2 antagonist domperidone (2 mg/kg IP), but not by the D1 antagonist SCH 23390 (1 mg/kg IP). The apomorphine-induced decrease in adrenal catecholamine concentration was suppressed by denervation of the adrenal medulla, i.e. unilateral section of splanchnic fibers performed 5 days before. These results show that, under our experimental conditions, the effect of apomorphine is due to the activation of D2 dopamine receptors probably located on splanchnic nerve endings and suggest the existence of a peripheral D2 dopaminergic system which modulates adrenal medullary catecholamine content.

Adrenal Medulla↗
PubMed1989

Calcium antagonists and the vestibular system: a critical review of flunarizine as an antivertigo drug.

Flunarizine, a diphenylalkylamine, is one of the most popular antivertiginous drugs used nowadays in France. However, until now, there are very few preliminary data about the physiological or pathophysiological functions of calcium in the vestibular system. Moreover, experimental and clinical arguments are still insufficient to clearly demonstrate that 1) flunarizine is an effective antivertiginous drug and 2) this putative antivertiginous property is really due to the anticalcic action of the drug and not to a more classical antagonistic effect on H1 receptors. Much more work is needed before accepting the indication of any anticalcic drug as an effective antivertigo treatment.

Animals↗
PubMed1989

Involvement of a pertussis toxin-sensitive G-protein in the pharmacological properties of septo-hippocampal neurones.

1. The physiological and pharmacological properties of identified septo-hippocampal neurones (SHNs) have been studied in rats pretreated with the bacterial toxin, pertussis toxin (PTX). 2. In rats anaesthetized with urethane and pretreated with PTX, the axonal conduction velocity was unchanged while the mean spontaneous activity was significantly increased. 3. PTX pretreatment had no effect on responses of SHNs to the iontophoretic application of gamma-aminobutyric acid (GABA) and cholinoceptor agonists (acetylcholine or carbachol). 4. Baclofen and 5-hydroxytryptamine (5-HT), almost exclusively inhibitory in control rats, had little effect or an excitatory effect in PTX pretreated rats. 5. These results suggest the involvement of a pertussis toxin-sensitive G-protein in responses medicated by 5-HT and GABAB-receptors but not in responses mediated by cholinoceptors and GABAA-receptors in medial septum neurones projecting into the hippocampus.

Animals↗
PubMed1989

A randomised controlled study of bromocriptine versus levodopa in previously untreated Parkinsonian patients: a 3 year follow-up.

The long term effects of a de novo treatment with levodopa versus bromocriptine were compared in respectively 13 and 15 previously untreated patients with Parkinson's disease in a prospective randomised trial. Thirteen patients were treated with levodopa alone (mean dose 444, SEM 63 mg daily) whereas 15 others received bromocriptine alone (mean dose 50, SEM 6 mg daily) during 37, SEM 4 and 32, SEM 4 months respectively. For a similar decrease in the Columbia rating scale, the nature of long term side effects was different in the two groups: three patients on levodopa developed peak-dose dyskinesias and one other dystonia. With bromocriptine, one patient developed a severe psychosis whereas 3 others suffered from primary lack of efficacy (1 case) or late decrease in efficacy (2 cases). These results demonstrate the potential of D2 dopamine agonists (like bromocriptine) in the de novo treatment of Parkinson's disease; however, their use is limited by their lack of efficacy and/or the occurrence of neuropsychiatric side effects.

Bromocriptine↗