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C Chavoix

Publications and source records attributed to C Chavoix.

At least 19 recordsLinked to original sources
PubMed2000

Cognitive processes involved in delayed non-matching-to-sample performance in Parkinson's disease.

Visual recognition memory was assessed in terms of delay duration, memory load and amount of interference(s) in non-demented patients with Parkinson's disease (PD) using an automated delayed non-matching-to-sample (DNMS) task with trial-unique stimuli. Special attention was focused on the different cognitive functions engaged by these patients in solving this recognition memory task. Thirteen patients with PD, carefully selected according to their stable regimen and anticholinergic medication, were compared to 12 controls matched by age and educational level. Besides the DNMS task, a neuropsychological battery that included tasks carefully selected according to processes potentially required to perform the DNMS task (e.g. attention, executive functions, visual discrimination and motor speed) was administered to the subjects. As compared with controls, patients with PD showed a deficit on most DNMS subscores, except those requiring the least cognitive load. The correlative analysis between the DNMS and other neuropsychological tasks suggests involvement of long-term memory mainly in the DNMS performance for the control group, contrasting with a major involvement of executive functions for the patients with PD. These data indicate that visual recognition memory impairment in non-demented patients with PD is largely due to an executive dysfunction, notably in working memory. Several hypotheses are proposed concerning the neuronal substrates underlying the impairment on the visual DNMS task in PD.

Adult↗
PubMed2000

Mapping the visual recognition memory network with PET in the behaving baboon.

By means of a novel 18F-fluoro-deoxyglucose PET method designed for cognitive activation imaging in the baboon, the large-scale neural network involved in visual recognition memory in the nonhuman primate was mapped for the first time. In this method, the tracer is injected in the awake, unanesthetized, and unrestrained baboon performing the memory task, and brain imaging is performed later under light anesthesia. Brain maps obtained during a computerized trialunique delayed matching-to-sample task (lists of meaningless geometrical patterns and delay > 9 seconds) were statistically compared pixel-by-pixel to maps obtained during a specially designed visuomotor control task. When displayed onto the baboon's own anatomic magnetic resonance images, foci of significant activation were distributed along the ventral occipitotemporal pathway, the inferomedial temporal lobe (especially the perirhinal cortex and posterior hippocampal region), and the orbitofrontal cortex, consistent with lesion, single-unit, and autoradiographic studies in monkeys, as well as with activation studies in healthy humans. Additional activated regions included the nucleus basalis of Meynert, the globus pallidus and the putamen. The results also document an unexpected left-sided advantage, suggesting hemispheric functional specialization for recognition of figural material in nonhuman primates.

Animals↗
PubMed1999

Combined use of T1-weighted MRI and MRA for stereotaxic lesioning of the nonhuman primate brain: application to the rhinal cortex.

Stereotaxic brain lesioning is widely used to develop experimental models of human brain disease in the nonhuman primate. To avoid intraoperative vascular complications such as intracranial hemorrhage, we developed a methodology that is easy to implement. This method combines T1-weighted magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). This technique is applied to produce bilateral neurotoxic lesions of the rhinal cortex, a structure located medially in the temporal lobe, in eight baboons (including five sham-operated animals with needle descents but no ibotenic acid injection). Two other baboons were lesioned before the MRA technology was available. The MRA sequence (two-dimensional time-of-flight, axial acquisition) was used to localize the blood vessels in the needle trajectories, i.e., the highly vascularized sylvian fissure and temporal gyri. The vessel coordinates were transposed onto the coronal MRI-TI images, onto which the injection sites were determined and the planned needle tracks drawn. In the eight baboons that had MRA, 26.8% of these needle tracks had to be slightly displaced because of the presence of blood vessels. The stereotaxic coordinates of the final target sites were then calculated with respect to six skull landmarks that also served as a reference during surgery. No intracranial hemorrhage occurred in any of the eight baboons in which MRA was performed, in contrast to one of the two baboons not studied with MRA. The histological analysis showed a good extent of the rhinal lesions in all lesioned animals, with minimal damage to areas other than those that were targeted. Thus, combined use of MRI-TI and MRA proved to be reliable in reducing vascular complications, affording new advances for stereotaxic surgery in nonhuman primates.

Animals↗
PubMed1999

Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET. Implications for Alzheimer's disease.

Temporoparietal glucose hypometabolism, neuronal loss in the basal forebrain cholinergic structures and preferential accumulation of neurofibrillary tangles in the rhinal cortex (i.e. in the entorhinal and perirhinal cortices) are three early characteristics of Alzheimer's disease. Based on studies of the effects of neurotoxic lesions in baboons, we previously concluded that damage to the cholinergic structures plays, at best, a marginal role in the association neocortex hypometabolism of Alzheimer's disease. In the present study, we have assessed the remote metabolic effects of bilateral neurotoxic lesions of both entorhinal and perirhinal cortices. Using coronal PET coregistered with MRI, the cerebral metabolic rate for glucose (CMR(glc)) was measured before surgery and sequentially for 2-3 months afterward (around days 30, 45 and 80). Compared with sham-operated baboons, the lesioned animals showed a significant and long-lasting CMR(glc) decline in a small set of brain regions, especially in the inferior parietal, posterior temporal, posterior cingulate and associative occipital cortices, as well as in the posterior hippocampal region, all of which also exhibit glucose hypometabolism in Alzheimer's disease. Remarkably, the degree of CMR(glc) decline in four of these regions significantly correlated with the severity of histologically determined damage in the rhinal cortex, strongly supporting the specificity of the observed metabolic effects. There were also differences between the metabolic pattern observed in the lesioned animals and that classically reported in Alzheimer's disease; for instance, the hypometabolism we found in the stratum has not been reported in early Alzheimer's disease, although this structure can be affected in late stages of the disease and has direct anatomical connections with the rhinal cortex. Nevertheless, this study shows for the first time that the temporoparietal and hippocampal hypometabolism found in Alzheimer's disease may partly result from neuroanatomical disconnection with the rhinal cortex. This, in turn, further strengthens the hypothesis that neuronal damage and dysfunction in the rhinal cortices play a major role in the expression of Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Effects of damage to the basal forebrain on brain glucose utilization: a reevaluation using positron emission tomography in baboons with extensive unilateral excitotoxic lesion.

Neuronal loss in the basal forebrain cholinergic structures and frontotemporal hypometabolism are two characteristics of Alzheimer's disease, but their interrelations still are unsettled. We previously reported that unilateral electrolytic lesions of the nucleus basalis of Meynert in baboons were associated with marked but transient cortical hypometabolism. The current study reevaluates this issue using improved methodology. Baboons with unilateral ibotenic acid lesion of all three basal forebrain cholinergic structures (IBO group) were compared with sham-operated animals. The CMRglc was measured with high-resolution coronal positron emission tomography scanning coregistered with magnetic resonance imaging, before surgery and serially between 4 and 72 days afterward. Severe histologic basal forebrain damage and a decrease of more than 50% in cortical choline acetyltransferase activity were found postmortem in the IBO group. Transient and nonspecific hypometabolism was found in the needle track area in both groups. Compared with the sham-operated group, only marginally significant decreases in ipsilateral-contralateral CMRglc ratios were observed in the IBO group, affecting only 1 of 14 neocortical areas investigated (the anterior temporal cortex) at a single postsurgical time (day 14), and the posterior hippocampal region at days 14 and 38. Furthermore, there was no consistently significant correlation between ipsilateral-contralateral CMRglc ratios and cortical choline acetyltransferase activity values in any of the four regions analyzed. These results suggest that cholinergic deafferentation play at best a marginal role in the brain hypometabolism observed in Alzheimer's disease.

Alzheimer Disease↗
PubMed1992

In vivo visualization of central muscarinic receptors using [11C]quinuclidinyl benzilate and positron emission tomography in baboons.

The muscarinic antagonist, quinuclidinyl benzilate (QNB), labeled with carbon 11 was used as a radioligand to visualize in vivo by positron emission tomography (PET) the central muscarinic acetylcholine receptors (mAChR) in baboons (Papio papio). The binding characteristics of [11C]QNB showed its specific binding to central mAChR. [11C]QNB brain uptake was high in cerebral cortex and striatum, areas that are rich in mAChR, whereas it decreased rapidly in cerebellum, evidencing non-specific binding in this structure that is almost devoid of mAChR. These results are consistent with the known cerebral distribution of mAChR in primates. [11C]QNB specific cerebral binding was enhanced by pretreatment with methyl-QNB, a peripherally acting muscarinic antagonist. Specifically labeled binding sites alone were blocked by prior administration of dexetimide, a muscarinic antagonist. Specific radioactivity was driven out from mAChR-rich regions by atropine and dexetimide, drugs with high affinity for mAChR. This competition was stereospecific since only dexetimide, the pharmacologically active isomer of benzetimide, was able to compete with the radioligand on its binding sites. A relationship between the occupancy of [11C]QNB-labeled receptors by atropine or dexetimide and the concomitant induction of a pharmacological effect was also detected by simultaneous PET scanning and electroencephalographic recording. Since mAChR form an important part of choline receptors in the central nervous system, [11C]QNB appears to be a suitable radiotracer to monitor cerebral physiological or pathological phenomena linked to the cholinergic system in living subjects.

Animals↗
PubMed1991

In vivo bidirectional modulatory effect of benzodiazepine receptor ligands on GABAergic transmission evaluated by positron emission tomography in non-human primates.

The central type benzodiazepine receptor (BDZr), an allosteric modulatory site of the GABAA receptor-anion channel, has been shown in vitro to respond to drugs with positive efficacy (agonists), zero efficacy (competitive antagonists) and drugs with negative efficacy (inverse agonists). However, this general concept of the function of BDZr drugs has rarely been assessed in intact living brain. We report here in on a non-invasive in vivo assessment of the intrinsic efficacies of BDZr drugs in the brain of non-human primates. We have performed an in vivo simultaneous determination of fractional BDZr occupancy and the resulting pharmacological efficacies of the full agonist diazepam, the partial agonist bretazenil, the antagonist flumazenil (Ro15-1788), the partial inverse agonist Ro15-4513 and the full inverse agonist methyl beta-carboline-3-carboxylate (beta-CCM). Positron emission tomography (PET) was used to estimate fractional BDZr occupancy measured as the in vivo displacement in the brain of the positron emitter radioligand, [11C]flumazenil. Simultaneously, the proconvulsant or anticonvulsant efficacies of the BDZr drugs were measured as their abilities to facilitate or counteract the central effects of an infusion of pentylenetetrazol, a non-competitive GABA antagonist acting on the picrotoxin site of the receptor complex. This was measured using electroencephalographic recording (EEG). Our results show that, in vivo, the fractional receptor occupancy by a given drug is perfectly correlated with its resulting graded pharmacological effects, as predicted from the competitive drug receptor interaction theory. Furthermore, the slope of the relationship between fractional receptor occupancies and the resulting pharmacological effects (an index of intrinsic efficacy) strictly depends on the BDZr ligand considered. Diazepam displayed a strong positive intrinsic efficacy, and, in contrast, beta-CCM a marked negative one. Between these two extremes, the partially active drugs bretazenil and Ro15-4513, which required a large fractional receptor occupancy to produce significant anti- or proconvulsant effects, respectively, displayed only a weak intrinsic efficacy. Flumazenil did not produce any significant pharmacological effect. We observed that the in vivo intrinsic efficacies of diazepam, flumazenil and beta-CCM correlate with their intrinsic efficacies as measured by their modulatory effects on the GABA-dependent membrane chloride conductance in vitro. Thus, the intrinsic efficacies measured using PET and EEG are likely to reflect the different in vivo abilities of BDZr drugs to induce or stabilize the GABAA-benzodiazepine chloride channel in a given conformation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

In vivo benzodiazepine receptor occupancy by CL 218,872 visualized by positron emission tomography in the brain of the living baboon: modulation by GABAergic transmission and relation with anticonvulsant activity.

In vivo benzodiazepine receptor occupancy by increasing doses of CL 218,872 has been evaluated in the baboon Papio papio, using (11C) RO 15-1788 as specific radioligand and positron emission tomography as external detection system. Although BZR heterogeneity has been previously demonstrated in the brain of the living baboon using PET, we did not observe in our studies that CL 218,872 interacts preferentially with one of the BZR subtypes. The monophasic pattern of the dose dependent CL 218,872 displacement curve and the corresponding "in vivo Hill coefficient" near unity suggest that CL 218,872 binds in cerebral baboon cortex with a similar affinity with BZ1 as well as BZ2 subtypes. The anticonvulsant properties of CL 218,872 against bicuculline and allylglycine-induced seizures were correlated with benzodiazepine receptor occupancy by assessment of electroencephalographic activity during positron emission tomography studies. Our data confirmed in vivo the hypothesis of a partial agonist anticonvulsant activity of CL 218,872. At the same time, the use of a GABA-antagonist (bicuculline) or an inhibitor of the GABA synthesis (allylglycine) suggested the existence of an allosteric interaction between benzodiazepine receptors and GABA receptors.

Allylglycine↗
PubMed1990

Interaction of suriclone with central type benzodiazepine receptors in living baboons.

The interaction of suriclone and two of its main metabolites with central type benzodiazepine receptors, which had been labeled in vivo with the radioligand [11C]RO 15-1788, was investigated in living baboons. The concentration of radioligand bound to the receptors, as measured in brain transverse sections by positron emission tomography, decreased rapidly after the i.v. administration of suriclone at doses known to induce pharmacological effects. The rate and extent to which [11C]RO 15-1788 binding was displaced increased with increasing doses of suriclone. The half-inhibitory dose (ID50) was determined to be 0.08 mg/kg in vivo. The rapid inhibitory effect of suriclone on the in vivo binding of [11C]RO 15-1788 in the brain seems to reflect its ability to act at the GABA-benzodiazepine receptor complex, at or near to the benzodiazepine binding site, to induce its pharmacological activity. The i.v. injection of the demethylated metabolite of suriclone, RP 35,489, only caused a slight displacement of [11C]RO 15-1788 binding even at a dose of 2 mg/kg. Thus, suriclone appears to be more potent than RP 35,489 to displace the benzodiazepine 11C antagonist in vivo. The sulfoxide metabolite, RP 46,166, did not significantly change the kinetics of [11C]RO 15-1788 binding in the brain. The slight effects produced by high doses of RP 35,489 and RP 46,166 on [11C]RO 15-1788 binding in the brain suggest that these metabolites are probably not responsible for the expression of biological activity of suriclone mediated by benzodiazepine receptors.

Animals↗
PubMed1990

Positron emission tomography study of brain benzodiazepine receptors in Friedreich's ataxia.

Central type benzodiazepine receptors were studied in 9 patients with Friedreich's ataxia and 12 healthy subjects using positron emission tomography (PET) and [11C]Ro 15-1788, a specific antagonist of the central type benzodiazepine receptors, as radioligand. A standard PET procedure was used in 5 patients and 8 controls to obtain brain kinetics of the total binding of the radioligand. The remaining subjects were intravenously injected with a saturating dose of unlabeled Ro 15-1788, 30 minutes after the tracer injection, to determine the nondisplaceable binding of [11C]Ro 15-1788. A semi-quantitative method was used to quantify the [11C]Ro 15-1788 data. None of the quantification indices in the cerebellar hemispheres, or in the other brain areas investigated, was significantly modified in patients with Friedreich's ataxia. These findings suggest that brain benzodiazepine receptors are unaffected in Friedreich's ataxia.

Adult↗
PubMed1990

Effects of unilateral lesion of the nucleus basalis of Meynert on brain glucose utilization in callosotomized baboons: a PET study.

Prior work has demonstrated that unilateral lesions of the nucleus basalis of Meynert (NbM) in baboons induce a marked reduction in glucose utilization of the ipsilateral cerebral cortex, linearly proportional to the depression in cortical choline acetyltransferase (ChAT) activity achieved. Unexpectedly, there was also marked hypometabolism of the contralateral cerebral cortex, and glucose utilization recovered gradually on both sides despite persistent deficit in cortical ChAT activity. To investigate the role of the corpus callosum (CC) in this bilateral metabolic effect and subsequent recovery, three baboons were subjected to unilateral electrolytic NbM lesion greater than 3 months following section of the anterior CC. Brain glucose utilization was sequentially studied by positron emission tomography; ChAT activity was measured and histological sections obtained after death. In these animals, the NbM lesion also induced significant metabolic depression over the ipsilateral cortex, proportional to the reduction in ChAT activity. Corpus callosotomy did not prevent the contralateral metabolic effects, suggesting that the latter do not normally operate through the CC. However, there was no significant recovery of glucose utilization, suggesting that, following unilateral NbM lesion, the CC normally mediates, at least in part, the recovery of cortical glucose utilization.

Animals↗
PubMed1990

Effects of anterior corpus callosum section on cortical glucose utilization in baboons. A sequential positron emission tomography study.

Cortical glucose utilization was measured under light anaesthesia using positron emission tomography and 18F-fluorodeoxyglucose before and serially after stereotaxic anterior corpus callosum section in 3 adult baboons (Papio papio); in 1 animal needles were introduced but callosotomy was not performed ('sham' operation). Lesion efficacy was verified by x-ray computerized tomography and by postmortem examination which indicated effective anterior two-thirds callosal section in all 3 baboons, as well as a small contusional area in the medial frontal cortex. A two-way layout analysis of variance performed on the regional cerebral metabolic rate of glucose (CMRGlc) data obtained in the frontotemporal, temporal and occipital areas revealed significant effects for both the time and the region factors (P less than 0.00001 for each); the time effects indicated a significant initial metabolic depression (P less than 0.01) at day 11 and 18, and a subsequent recovery (P less than 0.01 to 0.05) at day 98. Average CMRGlc changes from preoperative values at successive studies were -23%, -27%, -17%, -8% and +2%, and -17%, -21%, -10%, -5% and +6% in the 'surgically approached' and the contralateral frontotemporal area, respectively. The frontotemporal/occipital CMRGlc ratio was significantly depressed at days 11, 18 and 32 (P less than 0.01, 0.01 and 0.05, respectively), indicating a transient postoperative alteration in the cortical metabolic pattern. In the 'sham' animal, surgery induced negligible metabolic effects. Our results indicate that effective anterior corpus callosum section induces a transient bilateral depression of cortical metabolism, which predominates in the anterior parts of the brain, while metabolic recovery suggests efficient neuronal adaptation. These functional effects in the cortex may underlie the transient behavioural changes that follow anterior callosotomy in man.

Animals↗
PubMed1990

Quantitative evaluation of benzodiazepine receptors in live Papio papio baboons using positron emission tomography.

The binding of the 11C-labeled benzodiazepine antagonist Ro 15-1788 (flumazenil) was measured in the neocortex of live Papio papio baboons by positron emission tomography. This allowed us to calculate in vivo (i.e., at physiological temperature, neurotransmitters concentrations, and ionic environment) the apparent density of available benzodiazepine receptors (B'max) and the dissociation constant of Ro 15-1788 (Kd). By coadministering increasing doses of unlabeled Ro 15-1788 with [11C]Ro 15-1788 and assuming that nonsaturable radioactivity indicated the free ligand concentration, we were able to obtain saturation isotherms. We showed that a state of quasiequilibrium was reached 50 min after the administration of the radioligand. Linear Scatchard plots allowed us to calculate B'max at 78 and 50 pmol/ml of cerebral tissue in the occipital and frontal cortices, respectively. In both these areas, Kd is on the order of 6 nM, with a Hill number very close to unity. This indicates that Ro 15-1788 binds in vivo with high affinity to an homogeneous population of saturable sites. A similar measurement was carried out on a naturally photosensitive P. papio baboon. Absolute values of B'max, Kd, and Hill number were similar to those of the control baboons. Although results concerning this baboon can only be considered as a case report, this similarity may suggest that its epileptic syndrome is not related to a large change in B'max or Kd, at least in occipital and frontal cortices. Our results showed that quantitative estimation by positron emission tomography of some characteristics of benzodiazepine receptors is possible in live baboons and may represent a supplementary tool for investigating further the molecular mechanisms of benzodiazepine receptor function in physiological and physiopathological conditions. We suggest that a similar method of quantification of classic in vivo [3H]Ro 15-1788 binding could be usefully adapted when studying rodent models of epilepsy, stress, and other neuropsychological disorders. On the other hand, the similarity between the B'max and Kd values we obtained in baboons and those recently reported in humans using similar methods emphasizes that most of the in vivo characteristics of the benzodiazepine receptors of baboons are very close to those of human benzodiazepine receptors. This confirms that P. papio baboons are a suitable animal model for studying the pharmacology of benzodiazepine receptor ligands before clinical applications in humans.

Animals↗
PubMed1989

Anticonvulsant activity of the diaryltriazine, LY81067: studies using electroencephalographic recording and positron emission tomography.

It is reported that LY81067, a new diaryltriazine, possesses anticonvulsant properties against grand mal status epilepticus induced by intravenous administration of picrotoxin binding site ligands (Ro 5-4864 and pentylenetetrazole) in the baboon. Intravenous administration of LY81067 during the seizures blocked grand mal type electroencephalographic (EEG) paroxysmal discharges and led to a long electrical silence, progressively replaced by spike-and-wave discharges of low frequency (2 c/sec). A transient blocking effect was also observed when LY81067 was injected during grand mal status epilepticus induced by the benzodiazepine inverse agonist methyl beta-carboline-3-carboxylate; however, the long electrical silence observed after administration of LY81067 was rapidly followed by grand mal type paroxysmal discharges in the EEG, which could be stopped by a subsequent injection of Ro 15-1788. However, LY81067 also displayed intrinsic epileptogenic properties. Administration of this drug alone led to the appearance of rhythmic EEG (2-3 c/sec) associated with myoclonia. Concomitantly with the EEG studies, interactions of all these drugs with benzodiazepine receptors were observed in vivo using [11C]Ro 15-1788 as radioligand and positron emission tomography (PET) as a non-invasive technique to measure the binding of the [11C]benzodiazepine antagonist in brain, in vivo. The [11C]Ro 15-1788 bound in the brain could not be displaced by the administration of LY81067 but rather, the [11C]antagonist binding in the brain was somewhat enhanced. Administration of pentylenetetrazole or Ro 5-4864 decreased the rate of wash-out of the radioligand. This fast effect of these two convulsant drugs was partially inhibited by the subsequent administration of LY81067. The concomitant blocking of the grand mal status epilepticus was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Benzodiazepine receptors studied in living primates by positron emission tomography: antagonist interactions.

After labelling the brain benzodiazepine receptors of sub-human primates with [11C]RO15-1788, the interactions of different benzodiazepine receptor antagonist ligands were studied by positron emission tomography (PET). Various doses of either RO15-1788, RO15-3505 or propyl beta-carboline-3-carboxylate were injected intravenously 20 min after the radiotracer, and induced an immediate and specific dose-dependent displacement of the brain radioactivity. However, a comparison of the dose-receptor occupancy patterns of these three antagonists established from the displacement experiments revealed that only propyl beta-carboline-3-carboxylate displayed clear biphasic dose-receptor occupancy curves. This indicates that, in the living primate brain, there are two different benzodiazepine receptor subpopulations (which can be either different benzodiazepine receptor subtypes or distinct conformational states of a single receptor).

Animals↗
PubMed1988

Status epilepticus induced by pentylenetetrazole modulates in vivo [11C]Ro 15-1788 binding to benzodiazepine receptors. Effects of ligands acting at the supramolecular receptor complex.

Positron emission tomography (PET) was used to investigate, in the living baboon, the in vivo modulation of [11C]Ro 15-1788 binding to benzodiazepine receptors in brain and the changes with ligands acting at the supramolecular complex during status epilepticus induced by pentylenetetrazole. The central type benzodiazepine receptors were labelled in vivo by intravenous injection of [11C]Ro 15-1788. Simultaneous positron emission tomography and electroencephalographic activity recording evidenced a modulation of the brain binding of [11C]Ro 15-1788 during pentylenetetrazole-induced status epilepticus. We investigated the changes in the modulation of radioligand kinetics and in seizure activity after intravenous administration of a benzodiazepine agonist (diazepam, 1.5 mg/kg), a benzodiazepine antagonist (Ro 15-1788, 2 mg/kg), a GABA agonist (progabide, 50 mg/kg) and a ligand of the picrotoxin/barbiturate binding sites (LY81067, 3.5 mg/kg). The results showed that there is an in vivo competitive interaction of pentylenetetrazole with the benzodiazepine receptors, as reflected by the low displacement of [11C]Ro 15-1788 in the first 10 min of the status epilepticus. However, in contrast to diazepam, progabide and LY81067, a dose (2 mg/kg) of Ro 15-1788 that saturates the benzodiazepine receptors was unable to block the seizures induced by pentylenetetrazole. This indicates that the benzodiazepine receptors play only a minor role in the status epilepticus induced by pentylenetetrazole. The contribution of other binding sites within the supramolecular complex is assessed.

Animals↗
PubMed1988

Regional specific binding of [11C]RO 15 1788 to central type benzodiazepine receptors in human brain: quantitative evaluation by PET.

The central type benzodiazepine receptors were studied in 17 healthy human subjects with 11C-RO 15 1788 and positron emission tomography (PET). The brain regional distribution of the tracer in eight control studies performed after injection of trace doses of 11C-RO 15 1788 was consistent with that of benzodiazepine receptors. Saturation studies with co-injected cold RO 15 1788 in the remaining subjects showed a dose-dependent decrease of brain radiotracer until full inhibition of specific binding was achieved with doses above 0.1 mg/kg (four studies). Based on the results, a simple method to estimate the specifically bound 11C-RO 15 1788 regionally in a single PET study is proposed, using the data from the full-saturation studies as a stable estimate of the nondisplaceable radioligand concentration. Using this method, it was found that quasiequilibrium between the estimated specifically bound and nondisplaceable components was achieved at times equal to or longer than 20 min after tracer administration. The validity of this method was partly supported by further results, showing a good agreement between the regional specific binding so calculated and postmortem data of receptor density.

Adult↗