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At least 1,099 records · Page 61Linked to original sources
PubMed1984

The staircase test in mice: a simple and efficient procedure for primary screening of anxiolytic agents.

The staircase test consists of placing a naive mouse in an enclosed staircase with five steps and observing the number of steps climbed and rearings made in a 3-min period. All the clinically active anxiolytics tested (chlordiazepoxide, clorazepate, diazepam, lorazepam, meprobamate, phenobarbital) reduce rearing at doses which did not reduce the number of steps climbed. The majority of non-anxiolytic substances tested (haloperidol, chlorpromazine, imipramine, amitriptyline, amphetamine, morphine and carbamazepine) produced a parallel reduction of both behavioural variables. Ethosuximide had no effect on behaviour. The anticonvulsant sodium valproate produced an anxiolytic profile in this test, since it reduced rearing, while increasing step climbing. This result confirms the anxiolytic properties of valproate observed in other behavioural models. Our results indicate that the staircase test in mice is simple, rapid and selective for anxiolytics. The test is well suited for use as a primary screening method.

Animals↗
PubMed1982

Cumulative dose-effect curves in a conflict test with incremental shock.

Cumulative dose-effect curves were generated for chlordiazepoxide, diazepam, meprobamate, pentobarbital, morphine, and d-amphetamine in a Geller-Seifter conflict test with incremental shock. The anxiolytics increased responses in conflict significantly at one or more doses, whereas the non-anxiolytics d-amphetamine and morphine produced dose-related decreases. Results were consistent with previous data from the conventional one-dose-per-session design.

Animals↗
PubMed1981

A water lick conflict paradigm using drug experienced rats.

A modified water-lick conflict paradigm is described, using trained rats for up to 35 weekly test sessions under 48 h of water deprivation. The rats rapidly became maximally suppressed by the punishment. This suppression was attenuated by the anxiolytics lorazepam, diazepam, phenobarbital, and meprobamate. The potentially anxiolytic drug CL 218872 and the anticonvulsant drug valproate sodium were also active. The antiserotonin drugs methysergide, cyproheptadine, cinanserin and parachlorophenylalanine were all inactive, as were several several other distinct classes of psychotropic drugs including propranolol, clonidine, THIP, theophylline, chlorpromazine, paroxetine and ethanol. The paradigm proved reliable, reproducible and useful for large scale investigations. Furthermore, it may provide means for detailed neuropharmacological and anatomical studies.

Animals↗
PubMed1982

Benzodiazepine antagonist Ro 15-1788: neurological and behavioral effects.

In neurological and behavioral studies in mice, rats, dogs and squirrel monkeys, the imidazobenzodiazepinone Ro 15-1788 acted as a potent benzodiazepine antagonist. The antagonistic activity was both preventive and curative and seen at doses at which no intrinsic effects were detected. It was highly selective in that it acted against CNS effects induced by benzodiazepines but not against those produced by other depressants, such as phenobarbitone, meprobamate, ethanol, and valproate. The onset of action was rapid even after oral administration. Depending on the animal species studied, the antagonistic effects lasted from a few hours to 1 day. The acute and subacute toxicity of Ro 15-1788 was found to be very low. Benzodiazepine-like effects were not seen.

Animals↗
PubMedDate not supplied

Oral activated charcoal in the treatment of intoxications. Role of single and repeated doses.

Activated charcoal has an ability to adsorb a wide variety of substances. This property can be applied to prevent the gastrointestinal absorption of various drugs and toxins and to increase their elimination, even after systemic absorption. Single doses of oral activated charcoal effectively prevent the gastrointestinal absorption of most drugs and toxins present in the stomach at the time of charcoal administration. Known exceptions are alcohols, cyanide, and metals such as iron and lithium. In general, activated charcoal is more effective than gastric emptying. However, if the amount of drug or poison ingested is very large or if its affinity to charcoal is poor, the adsorption capacity of activated charcoal can be saturated. In such cases properly performed gastric emptying is likely to be more effective than charcoal alone. Repeated dosing with oral activated charcoal enhances the elimination of many toxicologically significant agents, e.g. aspirin, carbamazepine, dapsone, dextropropoxyphene, cardiac glycosides, meprobamate, phenobarbitone, phenytoin and theophylline. It also accelerates the elimination of many industrial and environmental intoxicants. In acute intoxications 50 to 100g activated charcoal should be administered to adult patients (to children, about 1 g/kg) as soon as possible. The exceptions are patients poisoned with caustic alkalis or acids which will immediately cause local tissue damages. To avoid delays in charcoal administration, activated charcoal should be a part of first-aid kits both at home and at work. The 'blind' administration of charcoal neither prevents later gastric emptying nor does it cause serious adverse effects provided that pulmonary aspiration in obtunded patients is prevented. In severe acute poisonings oral activated charcoal should be administered repeatedly, e.g. 20 to 50g at intervals of 4 to 6 hours, until recovery or until plasma drug concentrations have fallen to non-toxic levels. In addition to increasing the elimination of many drugs and toxins even after their systemic absorption, repeated doses of charcoal also reduce the risk of desorbing from the charcoal-toxin complex as the complex passes through the gastrointestinal tract. Charcoal will not increase the elimination of all substances taken. However, as the drug history in acute intoxications is often unreliable, repeated doses of oral activated charcoal in severe intoxications seem to be justified unless the toxicological laboratory has identified the causative agent as not being prone to adsorption by charcoal. The role of repeated doses of oral activated charcoal in chronic intoxication has not been clearly defined.(ABSTRACT TRUNCATED AT 400 WORDS)

Antidotes↗
PubMed2004

Entomotoxicology for the forensic toxicologist: much ado about nothing?

We present a series of 29 necropsies in which organic compounds (including benzodiazepines, barbiturates, antidepressants, phenothiazine, opiates, cannabinoids, meprobamate, digoxin and nefopam) were detected in arthropod larvae sampled on human corpses. No correlation was observed between drug concentrations in the larvae versus human samples. When tested, inter-larvae and inter-site variations of drug concentrations (i.e., within larvae when analyzed separately, and within anatomic sites when larvae were grouped according to their site of sampling) were enormous and not reproducible from one case to another, confirming that arthropod larvae are unreliable for quantitative toxicological analysis. Since drugs identified in maggots are always detectable in the cadaver too, we conclude that larvae analysis is of almost no interest for practical forensic casework.

Animals↗
PubMed2004

[Chronic temporomandibular disorders].

According to the 3rd German Oral Health Study (1999), the prevalence of painful temporomandibular disorders (TMDs) is about 5%. Although limited information about the magnitude of utilization of health care services and expenses for health care in temporomandibular pain patients is available, the financial burden of affected individuals may be considerable. The etiology and pathophysiology of chronic TMDs is still obscure. However, certain (patho)physiological mechanisms may be associated with the genesis and perpetuation of these musculoskeletal facial pains (e. g. disturbances in central nervous system processing; psychosocial factors; hormonal influences). Strong scientific evidence from the dental/medical literature is currently available for the following forms of TMD treatment and management: occlusal appliances (stabilization appliance), clonazepam, diazepam, meprobamate, EMG biofeedback, multimodal approaches (somatic and psychological pain management).

Chronic Disease↗
PubMed1988

Short latency somatosensory evoked potentials and brain-stem auditory evoked potentials in coma due to CNS depressant drug poisoning. Preliminary observations.

In patients in coma due to severe CNS depressant drug overdose the central somatosensory conduction time (CCT) after median nerve stimulation is prolonged and N20 is dispersed. Brain-stem auditory evoked potentials demonstrate delayed interpeak latencies (IPLs) I-III, III-V and I-V. This was observed in 4 out of 5 patients investigated after intake of an overdose of amitriptyline (2 cases), barbiturates, meprobamate and nitrazepam (one case each). Toxic levels of drug overdose were related to prolonged CCT and IPLs, whereas normal CCT and IPLs were found at therapeutic drug plasma levels. CCT, IPLs and dispersion of N20 decreased during the course of coma. All patients were successfully treated. It appeared that SSEP and BAEP investigations could make a distinction between a 'toxic' and a 'therapeutic' coma level in severe drug overdose. It further appeared that normalization of CCT and IPLs preceded clinical improvement.

Adult↗
PubMed1982

Differential antagonism of the anticonflict effects of typical and atypical anxiolytics.

Selected benzodiazepine and non-benzodiazepine agents were studied alone or in the presence of benzodiazepine antagonists in the shock-induced suppression of drinking (SSD) procedure in rats. The disinhibitory activity of chlordiazepoxide, CL218,872, zopiclone and CGS 9896 was antagonized by two benzodiazepine antagonists, RO-15-1788 and CGS 8216. In contrast, the disinhibitory activity of fenobam, meprobamate, phenobarbital and tracazolate was not antagonized by either RO 15-1788 and CGS 8216. From these data it is apparent that the anticonflict activity of agents that bind to benzodiazepine receptors is blocked by benzodiazepine antagonists. In contrast, the activity of anxiolytics that are not displacers are unaffected even at higher doses.

Animals↗
PubMed1986

Major tranquillizers can be distinguished from minor tranquillizers on the basis of effects on marble burying and swim-induced grooming in mice.

The effects of psychotropic compounds on grooming and burying were compared in mice. Burying behaviour was provoked by glass marbles and grooming was observed after 3 min swimming. Compounds with minor tranquilizing properties, such as diazepam, chlordiazepoxide, flunitrazepam, clonazepam, meprobamate and ethyl alcohol, were more effective in reducing burying than grooming. Drugs with an anticholinergic effect, e.g. scopolamine and atropine were also more effective against burying. A number of neuroleptic drugs, such as haloperidol, chlorpromazine, perphenazine and trifluperidol reduced grooming more effectively than burying. Non-selective inhibitory effects were observed with clozapine, thioridazine, diphenhydramine, imipramine, mianserin and apomorphine. It is concluded that, with certain limitations, the burying-grooming test described offers a simple tool for identifying novel compounds as potential major or minor tranquilizers.

Animals↗
PubMed1993

Shock-induced ultrasonic vocalization in young adult rats: a model for testing putative anti-anxiety drugs.

A putative animal model of anxiety based on shock-induced ultrasonic vocalization was pharmacologically validated in young adult rats. Suppression of shock-induced ultrasonic vocalization was obtained with diazepam, chlordiazepoxide, meprobamate and pentobarbital; the serotonin (5-HT)1A receptor agonists 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin], buspirone, ipsapirone, gepirone and tandospirone; the nonselective 5-HT receptor agonists TFMPP [1-(3-trifluoromethylphenyl)piperazin], mCPP [1-(3-chlorophenyl)piperazin] and DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane); the NMDA antagonists PCP (phencyclidine) and MK-801; the alpha 2-adrenoceptor antagonists idazoxane, yohimbine and 1-PP (1-pyrimidinylpiperazine); and the atypical neuroleptic clozapine. The alpha 2-adrenoceptor agonist clonidine, the 5-HT2/5-HT1C antagonist ritanserin, the 5-HT3 antagonists ondansetron and ICS-205,930, and the 5-HT reuptake inhibitor fluoxetine did not, or only partially, reduce ultrasonic vocalization. Tricyclic and tetracyclic, as well as some atypical antidepressants and a monoamineoxidase (MAO) inhibitor, showed no ultrasonic vocalization reducing effects, or reduced ultrasonic vocalization only at high doses. An opiate, an antimuscarinic, (pro)convulsants and typical neuroleptics did not reduce ultrasonic vocalization. The present findings suggest that the ultrasonic vocalization model specifically measures anxiolytic effects. Because ultrasonic vocalization responding develops within five days, remains stable for at least three months and gives highly reproducible results, the test appears suitable for rapid and repeated testing of new anxiolytics in the same animals.

Adrenergic alpha-Agonists↗
PubMed1988

CNS depressants accelerate the dissociation of 35S-TBPS binding and GABA enhances their displacing potencies.

The specific binding of 35S-t-butylbicyclophosphorothionate (TBPS) was studied in synaptosomal membranes of rat cerebral cortex. The displacing potencies of eleven CNS depressants and three convulsants were determined in the presence of 1 microM GABA and 10 nM R 5135. GABA enhanced the displacing potencies of depressants of most diverse chemical structures: diaryltriazine (LY 81067), pyrazolopyridine (etazolate), cinnamide, glutarimide, 2,3-benzodiazepine (tofizopam) and alcohol derivatives, barbiturates, (+)etomidate, methaqualone and meprobamate. In contrast, the IC50 values of convulsants (picrotoxinin, pentetrazol and the barbiturate enantiomer S(+) MPPB) were not significantly affected. The depressants accelerated either basal or GABA-augmented dissociation of 35-TBPS mainly by increasing the contribution of its rapid first phase.

Animals↗
PubMed1978

Despite various drugs, cats continue to kill mice.

Amphetamines (d- at 0.5--4 mg/kg; 1- at 2--4 mg/kg) inhibited spontaneous mouse killing by some, but not all cats. Various other drugs (drugs and maximum tested doses were: imipramine, 64 mg/kg; amitriptyline, 32 mg/kg; tranylcypromine, 2 mg/kg; tripelennamine, 4 mg/kg; scopolamine, 1 mg/kg; methyl scopolamine 1 mg/kg; chlordiazepoxide 16 mg/kg; diazepam 4 mg/kg; meprobamate, 80 mg/kg; pentobarbital, 16 mg/kg; chlorpromazine, 8 mg/kg; and haloperidol, 0.5 mg/kg) did not reliably inhibit such killing. In contrast with rats, mouse killing by cats was not consistently blocked by antidepressants or amphetamines. When individual cats were inhibited, their reduction of killing seemed related to anorexia rather than to affective arousal.

Aggression↗
PubMed1985

Non-benzodiazepine anxiolytics: potential activity of phenylpiperazines without 3H-diazepam displacing action.

Four phenylpiperazine derivatives exhibited an activity similar to benzodiazepines and meprobamate in the 4-plate test. One of these (compound IV) demonstrated anxiolytic like activity in a step-down avoidance technique, in electroshock induced aggression and in the staircase test. In contrast to benzodiazepines, compound IV was not anticonvulsant, myorelaxant or sedative. Confirmation of the anxiolytic activity of compound IV in animal models was obtained in 3 separate clinical trials in anxious patients. The mechanism of action of these phenylpiperazines appears to be different from the benzodiazepines as they do not displace 3H-diazepam binding nor do they interact with other elements of the GABA receptor macromolecular complex. Instead, compound IV interacts with both dopaminergic and serotoninergic neuron systems. Thus, from this data it would appear that an activity at the benzodiazepine recognition site is not obligatory for anxiolytic activity in man or in animals models.

Aggression↗
PubMed1988

Episodic barrel rotations induced by intrastriatal injection of quinolinic acid in rats. Inhibition by anticonvulsants.

Unilateral intrastriatal injection of quinolinic acid (2,3 pyridine dicarboxylate; QUIN) in the rat produces episodic barrel rotations and tonic-clonic forepaw movements, lasting for several hours. We investigated whether intraperitoneal posttreatment with anticonvulsants could abolish this phenomenon when it is already fully developed, and whether their potency ratio was similar in models of epilepsy. All 8 tested antiepileptics, namely carbamazepine, clonazepam, diazepam, diphenylhydantoin, ethosuximide, flunarizine, phenobarbital and sodium valproate decreased this behaviour in a dose-dependent way. Six other drugs with anticonvulsant properties were also effective: DL-2-amino-7-phosphonoheptanoic acid, desipramine, etomidate, ketamine, meprobamate and sabeluzole. The ED50-values for halving the frequency of the episodes of barrel rotation correlated well with published ED50-values for inhibition of tonic hindpaw extension in the maximal metrazol seizure test (rs = .95, p less than 0.001) and with the ED50-values for halving the duration of the forepaw clonus in the rat-kindling model (rs = .93, p less than 0.001). This quinolinic acid test allows visualization of the onset of action of anticonvulsants, with each animal as its own control. In order to assess whether this test is also sensitive to drugs influencing the symptoms of Huntington's disease, the effect of the dopamine antagonists haloperidol and pimozide, the acetylcholinesterase inhibitor physostigmine and the anticholinergics atropine and dexetimide were investigated as well. The experiments suggested that the barrel rotations and clonic forepaw movements, only 3-6 hours after intrastriatal injection of QUIN respond to anticonvulsants, but are not specifically sensitive to drugs used in the symptomatic treatment of Huntington's disease.

Animals↗
PubMed1992

Effect of various psychotropic drugs on the performance of avoidance and escape behaviors in rats.

The effect of different doses of nine psychotropic drugs upon conditioned avoidance responses (CARs) developed on a stable basis, after appropriate training, was investigated in rats and compared with their capacity to disrupt escape responses (ERs). Haloperidol (HAL), chlorpromazine (CPZ), morphine (MOR), pentobarbital (PENT), chlordiazepoxide (CDP), meprobamate (MPB), and amphetamine (AMPH) dose dependently inhibited both behaviors. Imipramine also disrupted CARs dose dependently, but did not affect ERs at maximal tolerated doses. Significant differences in the minimal effective doses, effective dose range, and time of onset and duration of action, as well as in potency, were observed. The quantitative determination of the level of selectivity, based upon the ratio ED50 escape failure/ED50 avoidance failure, indicated that all CNS depressants tested caused a selective inhibition of avoidance behavior. HAL was found to be the most specific, followed, in order, by CDP, MOR, CPZ, MPB, and PENT, whose ratio values were not significantly different. AMPH produced a nearly parallel impairment of both behaviors and quipazine only affected CARs at toxic doses. It is concluded that both neuroleptic and nonneuroleptic CNS depressant drugs have selective inhibitory effects on avoidance behavior. Data revealed differences that were more quantitative than qualitative.

Animals↗
PubMed1985

Anxiety, anxiolytics and brain stimulation reinforcement.

The premise of this review is that neuronal substrates of anxiety are amenable to investigation using brain stimulation techniques. Anxiolytics such as meprobamate and the benzodiazepines may enhance intracranial self-stimulation (ICSS) behavior. Although demonstrated by numerous investigators, this effect shows considerable variability between and within laboratories. Some of this variability is explained by sedative/muscle relaxant effects, which are dissociable from drug-induced increases in ICSS and which may mask these increases. The anticonvulsant actions of anxiolytic drugs are unlikely to account for the increases in ICSS. Rather, anxiolytics appear to increase ICSS by attenuating concurrent aversive properties of stimulation. Consistent with this explanation, anxiolytic drugs attenuate escape from aversive dorsal tegmental stimulation. The neuronal substrates of this centrally mediated escape behavior differ from those mediating footshock-induced escape. Barbiturates also enhance ICSS, possibly due in part to an excitatory component that is not involved in benzodiazepine action. Inverse benzodiazepine agonists attenuate ICSS behavior in a manner that cannot be explained by nonspecific performance impairment. These substances, however, may not necessarily enhance stimulation-induced aversiveness. A strategy is proposed to integrate brain stimulation studies with molecular approaches to anxiety. Specifically, stimulation of sites associated with fear induction or fear reduction may selectively alter the release of endogeneous anxiogens or anxiolytic substances.

Animals↗
PubMed1992

The future of 5-HT1A receptor agonists. (Aryl-piperazine derivatives).

At present the dominant position among anti-anxiety medications has changed from meprobamate to the benzodiazepine derivatives. In order to avoid benzodiazepine's (BZ) undesirable side effects such as impairment of psycho-motor function, memory impairment, low dose dependence and withdrawal symptoms, a third generation anxiolytic agent, buspirone, the focus of the aryl-piperazine group of anti-anxiety agents, has been introduced recently. Aryl-piperazine derivatives work as 5-HT1A receptor partial agonists and are known as serotonin normalizers. Therefore, they are expected to have not only an anxiolytic function but also an anti-depressant effect as well. A characteristic of the aryl-piperazine derivatives is that they have no sedative and muscle relaxant effects, and they do not have BZ's undesirable side-effects, especially in regard to withdrawal symptoms. However they have a rather weak anxiolytic action and a slow onset of action. Aryl-piperazine derivatives will not take the place of BZ, but the use of BZ and buspirone as bridge medications, making the most of the strong points of both, can be proposed as a way to compensate for their respective clisadvantages.

Animals↗