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Biomedical subjects

J R Boissier

Publications and source records attributed to J R Boissier.

At least 19 recordsLinked to original sources
PubMed1985

Effects of the new eburnamenine derivative RU 24722 on EEG recovery and cerebral energy metabolism after complete ischemia.

The influence of a new eburnamenine derivative RU 24722 [(3 beta, 14 alpha, 16 alpha)-(+/-)-14,15-dihydro-20,21-dinoreburnamenin -14-ol] on post-ischemic EEG recovery was studied in N2O anesthetized rats subjected to 1 min of global-compression cerebral ischemia. RU 24722 was compared with vincamine, dihydroergotoxine mesylate and nicergoline. Treatment with RU 24722 (2 mg/kg i.v.) significantly decreased the EEG recovery time and increased the electrocortical activity during the first phase of the post-ischemic recovery. Vincamine (2 mg/kg i.v.), dihydroergotoxine mesylate (0.5 mg/kg i.v.) and nicergoline (0.5 mg/kg i.v.) were devoid of activity. In an attempt to elucidate its mechanism of action, the influence of RU 24722 on changes in the cerebral metabolic energy reserves was studied in mouse brain after different periods of decapitation ischemia. The changes occurring during the first 10 s of ischemia were used to calculate the baseline cerebral metabolic rate (CMR). The activity of RU 24722 was compared with that of vincamine and pentobarbital. RU 24722 (10 mg/kg i.p.) significantly retarded glucose, phosphocreatine and adenosine triphosphate utilisation and lactate production. Vincamine (10 mg/kg i.p.) had no effect on cerebral energy substrates. Pentobarbital (100 mg/kg i.p.) markedly increased the tissue concentration of glucose and phosphocreatine and decreased lactate levels before and after ischemia. The improvement of EEG recovery suggests that RU 24722 may be therapeutically effective in cerebral insufficiency, and the decreased brain energy demand may be one of the mechanisms by which RU 24722 has a protective effect against cerebral ischemic damage.

Adenosine Triphosphate↗
PubMed1983

Comparative study of central dopaminergic properties of RU 29717 (N-propyl-9-oxaergoline) and pergolide.

RU 29717, a 9-oxaergoline derivative, has been compared with pergolide in a variety of biochemical and behavioural tests indicative of dopaminergic (DAergic) activity. RU 29717 and pergolide have a similar affinity for DA receptors labelled by [3H]spiroperidol or [3H]dihydroergocryptine ( [3H]DHEC) by using striatal or anterior pituitary membranes respectively. Both compounds stimulate the striatal DA-sensitive adenylate cyclase and inhibit the activity of this enzyme in dispersed cells from the neurointermediate lobe of the pituitary gland. In anterior pituitary cells in primary culture, they decrease prolactin release with the same efficacy. In vivo, they exert a long-lasting inhibition of the reserpine-induced hyperprolactinemia. They equally retard the alpha-MPT-induced disappearance of striatal DA and increase striatal acetylcholine levels. In behavioural models, the similarity between RU 29717 and pergolide is also evident: they induce contralateral circling in animals lesioned unilaterally with 6-OHDA, produce stereotyped behaviour and have emetic activity within the same dose range. Therefore, RU 29717, like pergolide, is a potent direct acting DAergic agonist. In experimental models used to investigate this activity at the striatal or the anterior pituitary levels the compounds present a similar profile of action.

Acetylcholine↗
PubMed1983

Synthesis and central dopaminergic activities of (+/-)-hexahydro-7H-indolo[3,4-gh][1,4]benzoxazine derivatives [(+/-)-9-oxaergolines].

The synthesis and biological activities of a series of (+/-)-hexahydro-7H-indolo[3,4-gh][1,4]benzoxazine derivatives [(+/-)-trans-9-oxaergolines] with central dopamine (DA) agonist properties are described. The compounds were prepared from [2aRS-(2a alpha,4 beta,5 alpha)]-4-amino-1,2,2a,3,4, 5-hexahydro-1-(phenylmethyl)benz[cd]indol-5-ol (6b) by alkaline cyclization of the corresponding N-chloracetamide 7b, followed by reduction of the amido group [5aRS-(5a alpha, 6a beta, 10a alpha)]-4,5,5a,6,6a,7,9, 10a-octahydro-4-(phenylmethyl)-7H-indolo[3,4-gh][1,4]benzoxazin-8-one (8b) with LiAlH4. After debenzylation of the resulting amine 9a, the indoline ring of [5aRS-(5a alpha, 6a beta, 10a alpha)]-4,5,5a,6,6a,8,9, 10a-octahydro-7H-indolo[3,4-gh][1,4 ]benzoxazine (10a) was dehydrogenated with MnO2 to give (+/-)-trans-9-oxaergoline (11a), which can be alkylated on the nitrogen (11b,c and 12) and brominated in position 2 (13a,b). The compounds were examined in vitro for their ability to bind to DA receptors and to inhibit prolactin (PRL) secretion in pituitary cells in culture, in vivo both for their DA stimulant effects at the striatal level (circling in 6-OHDA-lesioned animals, DA turnover, and stereotypy) and inhibitory effects on plasma PRL levels in rats, and for their emetic effects in dogs. Most of the tested compounds were active in these tests, and the potency of (+/-)-trans-6-n-propyl-9-oxaergoline (11c) was comparable to that of pergolide mesylate.

Animals↗
PubMed1980

Biochemical assessment of the central 5-HT agonist activity of RU 24969 (a piperidinyl indole).

The most potent compound of a series of piperidinyl indole derivatives which decrease 5-hydroxyindole acetic acid (5-HIAA) levels in rat brain-stem was chosen for further study on the neurochemistry of serotonin (5-HT) neurons. This derivative (RU 24969: 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl) 1 H indole, succinate) exerted a dose-dependent reduction in 5-HIAA concentrations in rat forebrain and brain-stem, which was of rapid onset and lasted for at lest 4 h. The decrease in 5-HIAA was apparently due to a decrease in 5-HT turnover since RU 24969 significantly diminished 5-HTP accumulation after RO 4-4602 administration, and 5-HIAA accumulation after probenecid treatment. Basal or 5-HT-stimulated adenylate cyclase activities in colliculi from new-born rats were unaffected by RU 24969. This compound increased serum prolactin and corticosterone levels in a dose-related manner. Together with previous behavioral observations and the potent displacement of [3H]-5-HT binding obtained with this series, the present data indicate that these new piperdinyl indole derivatives are likely potent 5-HT receptor agonists in rat brain.

5-Hydroxytryptophan↗
PubMed1980

Time course of apomorphine-induced circling behaviour after striatal dopamine receptor denervation.

The curve describing the time course of apomophine-induced circling behaviour in rats with a 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine (DA) pathway was studied with a microcomputerized rotometer. Up to a 2-week interval after lesioning, the contralateral circling response was a single bell-shaped curve but this gradually became a double-peaked curve after 4-5 months. At this time the bell-shaped curve was, however, restored by haloperidol pretreatment. It is concluded that the response of striatal DA receptors was modified either by the lesion of another neuronal system and/or that the absence of DA nerve endings induced changes in the striatal DA receptor itself.

Animals↗
PubMed1980

[Psychopharmacological profile of a new dopaminergic agonist, RU 24213 (author's transl)].

The psychopharmacological properties of RU 24213 were compared to those of other dopaminergic agonists (apomorphine, dexamphetamine, bromocriptine and L-dopa) in various behavioural tests. In naive mice the drug reduced the locomotor hyperactivity in the primary exploratory phase and produced stimulation in the subsequent stabilized activity period. In rats it provoked dose-related stereotypies, specially gnawing and sniffing. It delayed the cataleptic state induced by prochlorperazine without affecting its intensity. In animals unilaterally lesioned with 6-OHDA in the nigro-striatal pathway, RU 24213 caused contralateral turning. It exhibited relatively weak emetic and anorexic effects in dogs. Core temperature recordings in rats revealed a biphasic hypo- and hyperthermic activity. In drug interaction studies it was obsers in rats with unilateral electrolytical striatal lesion. The results obtained suggest that RU 24213 stimulates dopamine receptors both directly and indirectly. In this respect it could be compared to bromocriptine but unlike this latter compound it has an immediate effect which is of shorter duration.

Animals↗
PubMed1980

Comparative ototoxic effects of RU 25434, amikacin and neomycin in guinea-pigs.

The ototoxic effects of RU 25434, a new semi-synthetic aminoglycoside antibiotic, were compared to those of amikacin and neomycin. Experiments were performed in adult and new-born guinea-pigs, ototoxicity being assessed by Preyer's reflex response and the measurement of the cochlear microphonic potentials at the end of treatment. The well known ototoxicity of neomycin was observed and RU 25434 appeared to be relatively less toxic than amikacin. The use of new-born guinea-pigs seem to be particularly suitable for this type of study because of their apparent sensitivity to ototoxicity.

Age Factors↗
PubMed1980

beta-Adrenoreceptor blockage and genetic hypertension development in rats.

The effects of propranolol (100 mg/kg), atenolol (200 mg/kg) and acebutolol (1000 mg/kg) administered daily by gavage to spontaneously hypertensive rats (SHRs) from their 6th to 20th weeks of age were investigated on genetic hypertension development (GHD) and at regular intervals on heart rate (HR), cardiac output (CO), stroke volume (SV), peripheral resistence (PR), plasma renin concentration (PRC) and heart weight/body weight ratio (HW/BW). Treatment with propranolol and especially atenolol markedly inhibited GHD while acebutolol was ineffective. No correlation was found between GHD prevention and (1) the degree of beta-adrenergic blockade (2) the reductions in HR and CO and (3) the decrease in PRC induced by the three treatments. Although none of the three drugs prevented the progressive increase in PR which develops in SHRs during their growth, propranolol and atenolol opposed GHD mainly by reducing CO, this effect being however partly counterbalanced for atenolol by a secondary potentiation of PR increase. With acebutolol, a similar reinforcement of PR increase occurred which completely neutralized the reduction in CO, resulting in the drug's ineffectiveness against GHD. These differential effects of the three drugs probably reflect different early induced structural modifications at cardiac and/or vascular levels.

Acebutolol↗
PubMed1980

Bronchopulmonary effects of dopamine in the guinea-pig.

The effects of dopamine (DA) were studied in vivo on the pulmonary airway resistance of the unanaesthetized guinea-pig, and in vitro, on the isolated trachea of the same animal. DA relaxes the isolated trachea previously contracted by ACh, but only at very high concentrations (10(-4) to 10(-3) M) and appears to be approximately 7000 times less active than isoprenaline (ISO). The relaxation caused by DA is: (1) diminished by pretreatment with cocaine or reserpine indicating an indirect effect linked to a release of endogenous catecholamines; (2) increased by phentolamine, suggesting a masked contracting alpha-adrenergic component; (3) completely abolished by propranolol through competitive antagonism. In vivo, DA reduces the increase in pulmonary airway resistance provoked by ACh. Its action, which is mainly beta-adrenergic, is, nevertheless, 1.4 x 10(5) times less than that of ISO. Thus, dopaminoreceptors do not seem to exist in the tracheobronchial smooth muscle of the guinea-pig. DA only has partial beta-adrenergic agonistic action at that site.

Airway Resistance↗
PubMed1980

Antidopaminergic effect of estrogens at the striatal level.

The present study investigates the possibility that a potent synthetic estrogen (moxestrol) possesses an antidopaminergic effect at the striatal level. Moxestrol and other estrogens, but not progestagens, androgens or corticosteroids, blocked the apomorphine-induced increase in striatal acetylcholine (ACh) levels. This effect required the repeated administration of moxestrol to develop and lasted for at least 24 hr after the final moxestrol injection. Moxestrol-treatment alone did not alter striatal ACh levels nor did it affect striatal choline acetyltransferase or acetylcholinesterase activities. This estrogen did not modify either the basal or the apomorphine-induced decrease in striatal dopamine turnover. In rats with a unilateral 6-OHDA lesion of the nigro-striatal dopamine pathway, moxestrol antagonized the contralateral circling elicited by apomorphine. The effect of moxestrol on the apomorphine-induced increase in striatal ACh levels was abolished by hypophysectomy and mimicked by pituitary transplants under the renal capsule. These findings, together with previous clinical and pharmacological observations, strongly support the hypothesis that moxestrol exerts an antidopaminergic effect at the striatal level by decreasing dopaminergic postsynaptic transmission via mediation of the pituitary gland.

Acetylcholine↗