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PubMed1965

DRUGS, NEUROSIS AND THE FAMILY PHYSICIAN.

Many of the milder emotional disturbances, especially those which manifest themselves by vague physical symptoms, can be treated by physicians who are not psychiatrists. The stronger tranquilizing drugs, such as chlorpromazine, are not suited for most non-psychotic patients. If a patient is sick enough to require chlorpromazine, he should be referred to a psychiatrist. The newer antidepressant drugs are also mainly for severely depressed patients, and they also need a psychiatrist's care. There are many patients, however, who will respond to a mild tranquilizer, such as meprobamate, plus 10 to 20 minutes of discussion with the physician. Those who do not show definite improvement within ten interviews should be referred for psychiatric consultation. Most of the beneficial effects of drugs in non-psychotic patients are related to the attention and interest of the physician who prescribes them, and he should always take a few minutes to discuss the patient's problems with him.

Antidepressive Agents↗
PubMed1986

The staircase test: some evidence of nonspecificity for anxiolytics.

In the staircase test, a naive mouse is placed in a Plexiglas chamber containing a five-step staircase, and the number of rearings and steps climbed are recorded for 3 min. A claim for drug-class specificity has been made because conventional anxiolytics reduced rearings at doses that did not reduce steps climbed, while non-anxiolytics affected both measures in parallel. In the present study chlordiazepoxide, meprobamate, and ethanol registered the expected true positive effect by reducing rearings at doses that did not reduce steps climbed. Nicotine, which has some clinical anxiolytic action, registered a small true positive. The benzodiazepine anxiolytic alprazolam reduced both measures, a false negative, although it reduced rearings more than steps climbed. The putative novel anxiolytics CGS 9896, ketanserine, and tracazolate registered negatives, as did the known clinical anxiolytic buspirone. The non-anxiolytics phencyclidine and phenacetin registered true negatives, but morphine registered a clear false positive. The anxiogenics FG 7142 and pentylenetetrazol produced no significant effects. Because of the equivocal false negative for alprazolam, the clear false negative for buspirone, and the clear false positive for morphine, we concluded that the test lacks the degree of therapeutic-class specificity previously proposed but may still be useful in basic research.

Animals↗
PubMed1975

Experimental drug intoxication: treatment with charcoal haemoperfusion.

Dogs were given large doses of barbiturates, glutethimide, ethanol, methaqualone, ethchlorvynol, meprobamate, chloral hydrate, paracetamol and aspirin. These were treated by haemoperfusion using a column packed with charcoal coated with an acrylic hydrogel. Clearances for most drugs were significantly higher than those reported for haemodialysis. Minimal clearances of common biochemical entities were observed and although leucocyte and platelet counts were diminished, no deleterious effects attributable to this were encountered. Careful histological examination of tissues derived from perfused dogs revealed no evidence of charcoal emboli.

Acetaminophen↗
PubMed1975

Effects of personal interactions and setting on subjective drug responses in small groups.

Subjective responses induced by secobarbital and meprobamate were evaluated in 4 X 4 controlled trials in small groups of healthy young adults over 4 months. Drug effects were mainly influenced by attitudes toward the project, personal interactions, and anticipations of the subjects. The effects of some of these factors were similar to, and at least as powerful as those which are usually considered characteristic of sedatives and stimulants. The same factors, however, did not apparently effect objective responses.

Analysis of Variance↗
PubMed1978

Benzodiazepines and behavioral effects of reward (water) omission in the rat.

Two behaviors related to nonreward (omission of water in an enclosure where the rats were habituated to drink) were studied. The time spent licking the bottles during water omission and the time spent drinking during a subsequent 5-min drinking session (water available) were recorded. The drinking session was performed 30 min after the water-omission session. Rats subjected to water omission showed an enhanced drinking time that varied with the length of the water omission session, with the motivational state of the animals, and with the previous number of water-omission sessions. Diazepam, chlordiazepoxide, lorazepam, and meprobamate (i.p., 30 min before water omission), increased the time spent licking the empty bottles, but failed to abolish subsequently enhanced drinking. However, some of our data suggested that minor tranquilizers weakly reduced the increased drinking induced by nonreward, despite their direct stimulation on water drinking. It is proposed that either minor tranquilizers are devoid of general antifrustration activity or nonreward-induced frustration and nonreward-induced drive enhancement may not be correlated.

Amobarbital↗
PubMed1975

[Effects of antianxiety drugs on the food intake in trained and untrained rats and mice (author's transl)].

Various minor tranquilizers (benzodiazepines, barbiturates and meprobamate) induced an increase in the food intake of rats or mice. Drugs were injected i.p. 30 min before testing and the amount of food consumed during 30 min was recorded. The enhanced food consumption occurred when the animals were in a novel situation, in a situation which they had previously experienced, or in their home cage, in which they were used to eating in the daytime within 30 min. Studies with two benzodiazepines showed this effect to be maximal between 10 to 30 min after injection and to disappear 4 hrs after injection. Moreover, minor tranquilizers reduce the latency before eating of rats and mice tested in a new situation. These results and the observation of anti-anxiety drugs-induced hyperphagia in satiated animals suggest that: 1. The enhanced food consumption of a non familiar food in a novel situation induced by the minor tranquilizers could hardly be related only to their anti-anxiety action. 2. The existence of some inhibitory controls (endogenous satiety in daytime or satiety after recent absorption) is not essential for the action of the minor tranquilizers. 3. An increased motivation and a disruption in the food related behavior could possibly be an explanation for all the observed effects.

Amobarbital↗
PubMed1985

Diazepam-induced place preference conditioning: appetitive and antiaversive properties.

The place conditioning paradigm was used to examine the reinforcing properties of diazepam. Rats were injected with diazepam (0.5-5.0 mg/kg, IP) and 30 min later were confined for 30 min to one side of a shuttle box, in which each of the two compartments had distinctive features. On alternate (control) days they received vehicle injections and were confined for 30 min to the opposite side. At almost all doses tested, diazepam produced place preference for the distinctive compartment that had been previously associated with the drug. Preference for the drug side developed regardless of whether diazepam was paired or unpaired with the least-preferred side, and regardless of whether testing was carried out in the undrugged or in the drugged state. The rats preferred the drug side over a novel compartment, but they did not change their initial preference for the side when diazepam was given after removal from the training box. Animals injected with meprobamate (70 mg/kg, PO), a non-benzodiazepine anxiolytic, also developed conditioned preference for the drug side, comparable to that seen following cocaine hydrochloride (10 mg/kg, IP). The diazepam (2.5 mg/kg)-induced place preference was antagonized by CGS 8216 (3 mg/kg, IP), picrotoxin (2 mg/kg, IP) and naloxone (0.8 mg/kg, SC), injected 3 min before and 15 and 20 min after diazepam respectively. Sodium valproate (200 mg/kg, IP) did not influence diazepam (1 mg/kg)-induced place preference. Sodium valproate by itself had marginal effects on place conditioning. Picrotoxin and naloxone, but not CGS 8816, produced place aversion which, in the case of picrotoxin, was due to state dependent learning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

[Effects of antianxiety drugs on the water intake in trained and untrained rats and mice (author's transl)].

In water-deprived rats and mice, animals trained to the test situation spent more time in drinking than naive animals (first exposure to the test situation). The time spent in drinking, either during 5 min or during 10 min was recorded. As compared to controls, benzodiazepines, phenobarbital, meprobamate, and mecloqualone increased drinking time whether the experiments were run on naive or on experienced animals [5 or 10 (in mice) and 9 (in rats) exposures in the test situation]. All drugs were injected i.p. 30 min before testing. This release of the drinking behavior was more pronounced during the last 5 min than during the first 5 min of the 10 min test session. These results suggest that: 1. The inhibition of water intake of naive animals as compared to trained rats and mice, could be related to some emotional factors elicited by the first exposure to an unknown situation. 2. The increase in drinking time induced by the antianxiety drugs in a novel and in a familiar situation seems difficult to correlate only with the antianxiety action of these compounds. 3. Antianxiety drugs could interfere with the regulatory mechanism of thirst.

Animals↗
PubMed1975

Effects of various psychoative drugs on the metabolism of delta-tetrahydrocannabinol by rats in vitro and in vivo.

Metabolism of 14C-tetrahydrocannabinol (14C-THC) by rat liver microsomal preparations in vitro was studied in the absence and presence of other psychoative drugs. Disappearance of 14C-THC, and changes in metabolite patterns as shown by thin layer chromatography, were studied. SKF 525-A, pentobarbital, phenobarbital and amphetamine all produced an apparently non-competitive inhibition of THC metabolism. The inhibition produced by meprobamate was at least partly competitive. Morphine and mescaline had no evident effect. SKF 525-A and the barbiturates markedly decreased the concentrations of all the major THC metabolites found in the incubation media. In contrast, none of the drugs tested in vivo, with the exception of SKF 525-A, had any effect on the biliary 14C-excretion or metabolite pattern, or on final tissue levels of 14C, when administered in doses comparable to those used for studies of interaction with THC in vivo. SKF 525-A, however, did markedly decrease the excretion of total 14C and alter the pattern of THC metabolities in the bile, and increased the final tissue 14C levels. It is concluded that in vivo interactions between THC and other psychoactive drugs are probably not explainable primarily on the basis of altered THC metabolism.

Animals↗
PubMed1983

Effects of antianxiety and antipsychotic drugs on DRL responding for brain stimulation.

Satiated rats could be trained to give stable rates of responding for rewarding stimulation of the lateral hypothalamus delivered on differential reinforcement of low rate (DRL) schedule requiring 2 to 8 sec interresponse intervals for reinforcement (DRL-2 to 8). The performance on a DRL-8 schedule was tested 30 min after the oral administration of benzodiazepines. Diazepam (5 and 10 mg/kg) and meprobamate (200 mg/kg) caused significant increases in response rates during the first 5 min of a session, but not thereafter. Bromazepam (1 and 5 mg/kg) also caused a significant increase in the rates during the first and second 5 min. On the other hand, chlorpromazine (20 mg/kg) caused no effect in the first 5 min but decrease in second and third 5 min. These results indicate that DRL schedules with a brain stimulation reward provided a useful tool for evaluation of antianxiety drugs. The advantage of the brain stimulation reward over food reward is that the possible effects of the drugs on hunger motivation need not be considered.

Animals↗
PubMed1985

The non-sedating anxiolytic CGS 9896 produces discriminative stimuli that may be related to an anxioselective effect.

Sprague Dawley albino rats were trained to discriminate an internal stimulus associated with CGS 9896, a non-sedating pyrazoloquinoline that exhibits anxiolytic activity in animals. Classical anxiolytics (diazepam and meprobamate) and proposed anxiolytic drugs having low sedative potential (CL 218,872 and tracazolate) generalized to the CGS 9896 discriminative cue. The CGS 9896 cue appeared to be mediated by a pure anxiolytic action as previous research has shown that this compound does not produce sedation or muscle relaxation. As such, the CGS 9896 stimulus would have both research and clinical application in the investigation of selective anxiomodulation. This is the first report of discriminative stimuli established on one of the newer atypical anxiolytics in which the discriminative cue appeared related to an anxiolytic effect.

Animals↗
PubMed1979

A test of anxiety that distinguishes between the actions of benzodiazepines and those of other minor tranquilisers and of stimulants.

The effects of minor tranquilisers and of stimulant drugs were studied in the Social Interaction test of anxiety in which the illuminance and unfamiliarity of the test arena are manipulated. Acute administration of sodium phenobarbitone (25 mg/kg) was without effect. Acute administration of sodium phenobarbitone (35 mg/kg) and of meprobamate (60 mg/kg) produced sedation: both locomotor activity and social interaction were reduced. On the other hand, amphetamine sulphate (2 mg/kg) and caffeine citrate (20 mg/kg) reduced social interaction, but increased locomotor activity. Chronic administration dissociated the pattern of results produced by sodium phenobarbitone (35 mg/kg) from that produced by flurazepam (0.5 mg/kg). With chronic treatment (5 days) neither drug reduced motor activity, but whereas phenobarbitone increased social interaction regardless of the test illuminance and unfamiliarity, the increase produced by flurazepam was limited to the more stressful test conditions, i.e., when the arena was unfamiliar or brightly lit.

Amphetamine↗
PubMed1981

Neuropharmacologic specificity of a simple animal model for the behavioral actions of benzodiazepines.

A simple model system for the behavioral actions of benzodiazepines is analyzed for its dose-response predictiveness, using several benzodiazepines, and for its pharmacological specificity, using other non-anxiolytic classes of psychoactive drugs. The model demonstrates an increase in mouse exploratory activity between a brighty-lit open field and a small, dark compartment by clonazepam, diazepam, flurazepam, chlordiazepoxide and meprobamate, but not by the peripheral benzodiazepine R05-4864, nor by clorgyline, butriptyline, or chlorpromazine.

Animals↗
PubMed1982

A sensitive and selective monkey conflict test.

A conflict model is described in which clinically effective antianxiety agents exhibit pronounced anticonflict activity. Male squirrel monkeys were trained to depress a bar for 5 sec to obtain food reinforcement. The 6 hr test session was comprised of an initial 3 hr period in which each 5 sec response was punished and then a 3 hr unpunished period. Trained monkeys would rarely be shocked and would make most of their responses during the non-punished period. Both benzodiazepine (chlordiazepoxide and diazepam) and non-benzodiazepine (meprobamate and phenobarbital) anxiolytics produced pronounced and unequivocal increases in punished responding. Other psychoactive agents (damphetamine, chlorpromazine, ethanol, morphine, amitriptyline and imipramine) did not produce an increase in punished responding. Sensitivity (i.e., large magnitude effects), selectivity, stable baseline performance and fully automated features make this test useful in identifying potential anxiolytic agents in primates.

Animals↗
PubMed1984

Oxazepam induced mouse killing by rats.

Oxazepam (2.5-80 mg/kg) induced significant mouse killing among large samples (N = 100/dose) of Holtzman strain albino rats. Meprobamate (2.5-80 mg/kg) and Chlorpromazine (0.5-4 mg/kg) did not induce killing. Despite its lesser tendency to induce aggression in humans, Oxazepam is as potent as Chlordiazepoxide for inducing killing by rats. Induction of mouse killing by rats appears to the predict clinical potency rather than the aggressive side-effects of anxiolytic benzodiazepines.

Aggression↗
PubMed1990

Drug discrimination in rats successively trained to discriminate diazepam and pentobarbital.

In Phase 1, rats were trained to discriminate either diazepam or pentobarbital from the no-drug condition. Diazepam, pentobarbital, triazolam, meprobamate, and zopiclone occasioned 100% drug-lever responding in tests under both training conditions; but the generalization gradients determined under the pentobarbital training condition were shifted to the right of those determined under the diazepam training condition. In Phase 2, the training drugs were reversed for the two groups, as well as which lever was paired with drug or no drug, in an effort to produce greater specificity of the Phase 2 discrimination. In Phase 2 tests, the Phase 1 training drug occasioned responding on the Phase 2 drug lever in all rats, suggesting that retraining overrode the Phase 1 discrimination. There were indications, however, that Phase 1 training influenced Phase 2 responding: 1) Rats ceased responding partway through no-drug training sessions using the former drug lever, and criterion performance was somewhat more difficult to maintain in Phase 2. 2) In Phase 2, dose-effect curves determined under pentobarbital training were shifted even further to the right of those determined under diazepam training than in Phase 1.

Animals↗
PubMed1983

Anxiolytics block excessive grooming behavior induced by ACTH1-24 and bombesin.

Diazepam and meprobamate significantly attenuated the increases in grooming behavior induced by peptides. Significant increases in total grooming frequency over a thirty minute observation period were produced by intraventricular administration of 1 microgram ACTH1-24 and by 1 microgram bombesin to awake rats. Diazepam 1 mg/kg IP blocked the peptide-induced increases in grooming. Non-sedating doses of diazepam also completely reversed the grooming seen when rats were placed in a novel environment. The functional antagonism between anxiolytics and stress-related peptides supports the concept of interacting brain mechanisms mediating stress and anxiety.

Adrenocorticotropic Hormone↗
PubMed1992

Use of antianxiety drugs as countermeasures in the detection of guilty knowledge.

To evaluate whether antianxiety drugs enable guilty subjects to appear innocent on polygraph tests, we compared the effects of diazepam, meprobamate, and propranolol on the outcome of a guilty knowledge test (GKT). Seventy-five undergraduate students were evenly divided among one innocent and four guilty groups. Subjects in each of the guilty groups received either one of the drugs or a placebo prior to the administration of the GKT and after viewing a videotape that depicted a burglary as seen from the perspective of the burglar. The results showed that drug status had no influence on the outcome of the GKT. Innocent subjects who coincidentally obtained high scores on a recognition memory test covering details of the mock crime tended to obtain higher guilt scores on the GKT.

Adolescent↗