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PubMed1986

Pharmacological studies on stress-induced increase in frontal cortical dopamine metabolism in the rat.

The effects of a variety of minor tranquilizers and of benzodiazepine inverse agonists on the stress-induced increase in frontal cortical dopamine metabolism have been studied in the rat. Electric footshock stress increased 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the frontal (but not parietal) cortex and in the nucleus accumbens but not in the striatum or ventral tegmental area. Similar stress-induced alterations of frontal cortical DOPAC levels were observed after DSP4-induced noradrenergic denervation or after adrenalectomy. Other types of stress, e.g. conditioned fear (exposure to an environment paired previously with footshock) or swim stress also provoked an elevation of DOPAC levels in the prefrontal cortex. When administered systemically, the anxiolytic agents meprobamate, CL 218,872, CGS 9896, suriclone and the hypnotic/anxiolytic drugs zolpidem and zopiclone all prevented the electric footshock stress-induced augmentation of cortical DOPAC levels whereas the gamma-aminobutyric acid receptor agonists progabide, muscimol and depamide or the sedative alpha-1 adrenoceptor antagonist prazosin were ineffective. The preventive effect of diazepam and zolpidem on the stress-induced biochemical response was antagonized by the benzodiazepine antagonist CGS 8216 but not by the gamma-aminobutyric acid receptor antagonist bicuculline. In nonstressed rats, systemic administration of the anxiogenic benzodiazepine inverse agonists beta-CCM (methyl-beta-carboline-3-carboxylate) and beta-CCE (ethyl-beta-carboline-3-carboxylate), but not of the benzodiazepine antagonists Ro 15-1788 or CGS 8216, caused an increase in frontal cortical DOPAC similar to that provoked by stress and which was antagonized by zolpidem.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Use of conditioned taste aversion as a conflict model: effects of anxiolytic drugs.

Moderate taste aversions were induced by pairing the initial consumption of 0.25% sodium saccharin (SACC) with either 25 mg/kg i.p. l-5-hydroxytryptophan or 30 mg/kg i.p. LiCl. The expression of these moderate conditioned SACC aversions was antagonized by pretreatments (i.p. or p.o.) with benzodiazepine and non-benzodiazepine anxiolytic drugs (lorazepam, diazepam, chlordiazepoxide, oxazepam, phenobarbital, meprobamate, and chlormezanone). Chlordiazepoxide produced less or no antagonism of the expression of stronger SACC aversions induced by 50 or 75 mg/kg l-5-hydroxytryptophan or by 60 or 90 mg/kg LiCl. Nonanxiolytic drugs, including dipsogenic compounds that increased the water intake of hydrated rats (2 M NaCl i.p.; isoproterenol HCl s.c.; and histamine diphosphate s.c.), and even additional 24 hr of fluid deprivation did not antagonize the expression of moderate conditioned taste aversions, indicating that anxiolytic drugs have a very selective effect and that they do not appear to act through homeostatic drinking mechanisms. An essential feature of the taste aversion conflict model is that thirsty rats encounter only SACC. When water was conspicuously available in addition to SACC in two-bottle tests, neither chlordiazepoxide nor phenobarbital antagonized the expression of conditioned taste aversion. Thus, anxiolytic drugs do not produce amnesia for the conditioned aversion, but attenuate the ability of conditioned SACC aversion to suppress SACC consumption in one-bottle tests. The antagonism of the expression of conditioned taste aversion measured with a one-bottle testing method offers a simple, sensitive, and selective screen for anxiolytic drugs. A possible mechanism by which anxiolytics increase both suppressed as well as unsuppressed fluid consumption is discussed.

5-Hydroxytryptophan↗
PubMedDate not supplied

[Effect of tranquilizers on impulse conduction in the afferent pathways of visceral nerves].

Experiments on pyrolaxon-immobilized cats evidence that diazepam produces depression of evoked potentials in the specific, nonspecific and associative brain structures upon an electric stimulation of the visceral and somatic nerves, and also with accoustic and photostimulation; Meprotan (meprobamate) in doses of 40-100 mg/kg neither changes nor increases, and in doses of 100-150 mg/kg, reduces the amplitude of evoked potentials and at the sme time forces down the arterial pressure. Amizyl (benactyzine) inhibits the potentials evoked by stimulation of the vagus. The amplitude of responses arising on stimulation of the inferior cardiac, celiac and sciatic nerves, and also with acoustic and photostimulation neither changes nor increases.

Animals↗
PubMed1979

Use of drugs with dependence liability.

The term addictive as used by the popular press frequently confuses the more precise concepts of acute and chronic tolerance, physical dependence and withdrawal, and psychologic dependence. Serious physical dependence on psychoactive drugs is rare and is easily managed. In contrast, psychologic dependence, the most important reason for persistent drug use, is much more common and is difficult to treat. Some tactics are available - for example, confrontation and discussion with the patient about how a drug is not going to be effective over long periods. Treating the symptom of a complex problem should, of course, not be expected to solve the problem. The most important tactic is to prescribe dependence-associated drugs only when clearly indicated, when the problem is responsive to drug therapy and for the shortest period necessary, without the option for renewing the prescription. Many problems related to drug use long after the period of expected benefit is past can be avoided by far more restrictive drug prescribing. Barbiturates and nonbarbiturate sedative hypnotics (e.g., ethchlorvynol, glutethimide, meprobamate, methaqualone and methyprylon) should not be prescribed for insomnia, acute reactive anxiety, chronic anxiety neurosis or depressive illnesses, since the safer and equally effective benzodiazepines, which are less associated with dependence, are available.

Amphetamines↗
PubMed1978

Effects of 3-trifluoromethyl-alpha-ethylbenzhydrol (RGH-3332), a new enzyme inducer, on the microsomal drug metabolism. Part I.

Intensity and duration of action of several compounds which are metabolized in the liver, are reduced in rats following pretreatment with 3-trifluoromethyl-alpha-ethylbenzhydrol (RGH-3332, Zixoryn), e.g., hexobarbital, methohexitone, glutethimide, hydroxymephenesine, chlorzoxazone, zoxazolamine, ketamine, chlordiazepoxide, diphenylhydantoin, ethylmorphine and pentylenetetrazol, hydroquinone, acenocumarol, respectively. Hypnotic effect of barbital is not altered by RGH-3332. Hexobarbital, meprobamate, mephenesine, nikethamide, canrenone, metyrapone, antipyrine, bromsulphophthalein, inocyanin green, bilirubin disappearance are enhanced, excretion of ascorbic acid is increased after RGH-3332 treatment. The effect of RGH=3332 is inhibited by D,L-ethionine. Hepatic cytochrome P450 concentration is increased following treatment with RGH-3332. Results of in vivo studies proved that 3-trifluoromethyl-alpha-ethylbenzhydrol has enzyme inducing activity.

Animals↗
PubMedDate not supplied

Drug use among college students--an interim report.

A survey was conducted at Agra (India) to study the extent and pattern of the non-medical use of dependence producing drugs among the post-graduate students of the local colleges and a number of medical students of other colleges of the state of Uttar Pradesh who were posted for training at the Mental Hospital. The study was confined to the academic year 1975-76 and covered 1,200 students. The present interim report is based on a sample of 564 students covered during 1975 (1st stage). The data on the total sample of 1200 (2nd and the final stage) are still being analysed. The results reveal that 73.88 per cent male, and 25.96 per cent female students had a drug experience at some time or another. Drug use was highest (80.66 per cent) among male medical students. The substances commonly used by males were: alcohol, barbiturates, Mandrax (methaqualone diphenhydramine hydrochloride). Vesparax (hydroxyzine hydrochloride), Equanil (meprobamate). Librium (chlordiazeproxide), pain killers (minor analgesics such as aspirin, and cannabis (bhang, ganja, and charas). The female students mainly used Equanil and pain killers. Among the 23 reasons offered for the use of drugs, the majority of students (50-59 per cent) stated that their main reason for drug use was "to relieve tension and facilitate relaxation". The next motivating factor for indulgence was "for the sake of fun" (30-39 per cent). The student drug users reported a number of effects produced by various substances. The most commonly mentioned effects were: excessive sleepiness, sluggishness, giddiness, inability to concentrate on studies, poor physical co-ordination. They expressed their opinion on various aspects of the drug use problem and favoured stringent measures to curb it.

Adolescent↗
PubMed1981

[Cross tolerance when benzodiazepines are administered with other substances].

It has been demonstrated in experiments on rats that only the drugs of benzodiazepine structure are responsible for complete cross tolerance as regards the myorelaxant effect under application with phenazepam. Other substances such as neuroleptics (chlorpromazine, triftazin), ethanol, phenobarbital, tranquilizers of non-benzodiazepine structure (meprobamate, ataractic), and an agonist of GABA receptors, muscimol, in doses that produce myorelaxation are not capable to replace phenazepam under conditions of this drug tolerance development. Partial cross tolerance under application with phenazepam arises from the use of supposed endogenous ligands of benzodiazepine receptors, nicotinamide and inosine, as well as of the use of the GABA-mimetic calcium valproate. The mechanisms of benzodiazepine tolerance development are discussed.

Animals↗
PubMed1983

[Effects of pentylenetetrazol on conflict behavior and interactions with anxiolytics in rats].

Effects of pentylenetetrazol (PTZ) on conflict behavior were studied using a punished water-lick (conflict) paradigm in rats. PTZ (5-20 mg/kg, ip) produced a dose-related enhancement of conflict behavior as demonstrated by a suppression of lick responding in low shock intensity (1.3-2.0 mA). Furthermore, PTZ (2-20 mg/kg, ip) clearly antagonized the release of punished responding induced by diazepam (5 mg/kg, ip), chlordiazepoxide (10 mg/kg i.p.) or meprobamate (75 mg/kg, ip) when a high intensity of shock (2.5 or 3 mA) was used. Bemegride also showed a similar suppressive effect on the anticonflict action of diazepam. However, bicuculline, picrotoxin or strychnine neither enhanced conflict behavior nor inhibited the anticonflict action of diazepam, even in high doses. In addition, PTZ (10 or 20 mg/kg, ip) did not show any significant effect on unpunished drinking or flinch-jump threshold, suggesting that the conflict enhancing action of PTZ may not be due to the secondary action including decrease in drive for drinking or increase in sensitivity to shock. These results suggest that PTZ may exert facilitation of conflict behavior or suppression of the anticonflict action of anxiolytics via an activation of the conflict generating mechanisms.

Animals↗
PubMedDate not supplied

[Mg2+-ATPase activity of brain mitochondria fractions in chronic stress and its correction by psychotropic agents].

The activity of Mg2+-ATPase was determined in the cortex mitochondrial fraction, limbic system and medulla oblongata under conditions of chronic stress as well as against a background of preliminary therapy by psychotropic drugs. At the inanition stage of animals the chronic stress is shown to inhibit sharply the process of respiration and phosphorylation (by dissociation) and to decrease the content of brain macroergs. The activity of Mg2+-ATPase in the mitochondrial fractions is lowered. It practically restores to the control level against a background of stress with preliminary course of administering nicotinic acid and GABA derivatives (lithonite, nicogamol and phenibut) to rats in average therapeutic doses. Mebicar, meprobamate and chlorodiazepoxide produce a less pronounced normalizing effect on the activity under study. It is substantiated to be expedient to apply psychotropic drugs as stress-protectors for normalization of energy metabolism of brain neurons.

Adenosine Triphosphatases↗
PubMed1984

Gangrene of the upper extremity following intra-arterial injection of drugs. A case report and review of the literature.

A case of inadvertent intra-arterial self-injection of crushed codeine tablets in an 37-year-old man, resulting in gangrene of an upper extremity, is presented. The problem studied was whether the gangrene was caused by the codeine or by one of the excipients found in the tablets. The cause of the gangrene was investigated in an experimental study. Each of the components of the tablet (codeine, lactose, gelatin, carboxymethyl cellulose, calcium stearate, talc, and microcrystalline cellulose) was injected into the femoral arteries of dogs. The results of the study clearly demonstrate that the unique component producing the gangrene was the micro-crystalline cellulose, while the injection of pure codeine was harmless. To date, the only reported deleterious effects of intravascular injection of micro-crystalline cellulose have been pulmonary embolism and granulomatosis. Some examples of drugs that include microcrystalline cellulose are methadone, methaqualone, oxcycodone, acetaminophen, aspirin with codeine, propoxyphene napsylate, meprobamate, and phenobarbital. Recently, the vulnerability of drug addicts who habitually inject drugs into veins to the accidental injection of an artery has been noted, and it seems likely that in the future the problem of intra-arterial injection will increase in severity. The literature of the last 40 years is reviewed, and a list of drugs known to have produced gangrene when injected intra-arterially is cited.

Adult↗
PubMedDate not supplied

Spectrophotometric determination of pentaerythritol tetranitrate in tablets.

A sensitive spectrophotometric method is reported for the quantitative determination of pentaerythritol tetranitrate in tablets. The method is based on reduction of pentaerythritol tetranitrate with zinc and calcium chloride, and reaction of the nitroso compound thus formed with 1-naphthylamine in acidic medium. The reaction gives a purple product having an absorbance maximum at 545 nm. Beer's law is obeyed in the concentration range of 1-10 micrograms/mL of reaction mixture. The presence of meprobamate in tablets does not interfere with the proposed analytical determination.

Calcium Chloride↗
PubMed1978

Fixed-bed charcoal hemoperfusion. Treatment of drug overdose.

Fixed-bed activated charcoal cartridges were used for hemoperfusion in the treatment of 54 patients with overdose of one or more drugs, including barbiturate, glutethimide, ethchloryvnol, meprobamate, methyprylon, methaqualone, salicylate, and diazepam. The most dramatic improvement was noticed in patients with phenobarbitol intoxication; they were admitted in stage 3-4 coma and were either awake or arousable by verbal communication at the end of 1 1/2 to 3 1/2 hours of hemoperfusion. Other intoxications improved slowly and required longer duration of treatment. The clearance rates of the drugs with hemoperfusion were greater than those usually achieved with hemodialysis. The data demonstrate the efficacy and usefulness of charcoal hemoperfusion for the management of drug overdose.

Adolescent↗
PubMed1981

Clinical experience with prolonged combined hemoperfusion-hemodialysis treatment of severe poisoning.

Fifteen patients with severe drug intoxication have been treated by a procedure combining hemoperfusion (HP, cellulose-coated activated charcoal, Adsorba C300, Gambro, Sweden) and hemodialysis (HD). The combined HP-HD treatment resulted in a clearance for amobarbital of 121 +/- 10 ml per min (mean +/-SEM), butobarbital 142 +/- 4 ml per min, carbromal 121 +/- 6 ml per min, hexobarbital 181 +/- 13 ml per min, meprobamate 145 +/- 9 ml per min, methaqualone 137 +/- 5 ml per min, phenobarbital 138 +/- 4 ml per min, and secobarbital 125 +/- 4 ml per min. There was no decrease in drug extraction even after 30 hours of treatment. Duration of treatment (6 to 33 hours) was determined by the clinical state of the patient. Prolonged HP-HD seemed to ben an efficient and sage procedure. Of 15 patients treated, 14 regained consciousness and 12 survived. The platelet count decreased, necessitating cessation of treatment in two cases. There was extraction of oxygen by the charcoal column, without influence on patient Po2. Glucose, urea, creatinine, uric acid, phosphate, and triglycerides were removed by adsorption on charcoal and/or dialysis.

Diuresis↗
PubMed1980

Biological evaluation of hemoperfusion in acute poisoning.

The efficiency of Hemoperfusion in acute poisoning cannot be clinically estimated, because: a) concomitant intestinal absorption, hepatic metabolism and urinary excretion must be taken into account. b) with supportive treatment alone, spontaneous recovery usually occurs in 98% of the intoxications in Intensive Care Units. The efficiency of hemoperfusion can only be estimated biologically. Measuring the blood level at the beginning and the end of hemoperfusion as well as measuring the clearances of the drug is misleading. A better method is to measure the amount of extracted drug, either indirectly by calculation (form hourly differences of arterio-venous measures of drug concentration multiplied by the blood flow) or directly by elution of the cartridge. In a practical way, if the blood level of drug is readily available after the patient is hospitalized, the optimum efficiency of hemoperfusion can be estimated beforehand, so that the decision to carry out the hemoperfusion can be maintained, postponed or abandoned. For the most part, the experience of toxicologists has shown hemoperfusion to be ineffective for drugs with weak extra-cellular distribution (such as Digitoxin, Tricyclic drugs, Heavy Metals, Colchicine). Its effectiveness for certain drugs, with poor in vitro dialysance (such as Paracetamol) or with small percentage of intestinal absorption (such as Paraquat) is still debatable. In the case of intoxications by hypnotic drugs, one hemoperfusion allows an average of 4 - 12% of the ingested medium and short barbiturates, 7 - 17% of the ingested Meprobamate. Whether these results can be judged satisfactory, life-saving or insignificant is largely a matter of personal standards.

Barbiturates↗
PubMedDate not supplied

[Chemotherapy in Alzheimer's disease. Retrospective study in a specialized hospital center].

In this study, our aim was to analyse the prescriptions of drugs used to improve Alzheimer's disease at CHS Paul Guiraud. This study was carried out a posteriori on 16 hospitalized patients. We have seen that for our patients there is no general rule, nor therapeutic scheme but the choice of treatment is carried out according to the professional experience of the physician. The treatment therefore is composed of symptomatic drugs alone or associated with etiologic drugs. Eleven anxiolytic or hypnotic drugs were prescribed. Alimemazine is the most prescribed in the sixteen cases. The preferential use of this drug can be explained by its presentation in the form of drops. In two cases, behavioural improvements were noted, in two other cases, we noted accentuation of dementia. Meprobamate used in seven cases of the sixteen, was never used alone. We find neuroleptics in fifteen of the sixteen cases studied: In seven cases they were administered from the beginning of the hospitalisation; for the others they were introduced later during a phase of agitation or delirium. On the whole, they were effective on aggressive agitation, in particular thioridazine. Eight of the patients, were treated with halopéridol. In two cases, the behaviour disorders were not stopped; in four cases, there was a worsening of dementia. We noted depression in 6 cases from the beginning of hospitalization, and two cases during hospitalization. The anti-depressive drugs besides their main effect, reduce also anxiety. In two cases, we observed an aggravation of disorientation and confusion following of the prescription of amitryptiline and mianserine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Drug-induced purpura simplex: clinical and histological characteristics.

Purpura simplex (PS) is a chronic condition manifesting as purpura, dermatitis and pigmentation. Histologically it is characterised by extravasation of erythrocytes and perivascular inflammation without fibrinoid necrosis. Most cases of PS are idiopathic. In order to determine if PS can be drug induced, a prospective study of 183 patients with PS was carried out. Of these, 27 patients were confirmed to be drug induced, as the purpura cleared on withdrawal of medications within four months. Lesions of drug-induced PS were significantly more generalised as compared to PS patients without a drug history. No epidermal involvement and an absence of lichenoid infiltrate characterised drug-induced as compared to idiopathic PS. NSAIDs, diuretics, meprobamate and ampicillin were the commonest offenders. We conclude that a drug-induced subgroup of PS exists and can be identified by clinical and histological features. Therefore, a careful drug history and skin biopsy are recommended in all cases of PS.

Drug Eruptions↗