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PubMed1983

[Regulation of oxidative phosphorylation as a possible method of normalizing cerebral metabolism].

Experiments were performed to study the effect of chronic emotional painful stress on oxidative phosphorylation in different structures of rat brain at varying times of the development as well as after pretreatment with psychotropic agents. During the stage of excess catabolism, stress was demonstrated to dramatically inhibit and dissociate oxidative phosphorylation. This led to the impairment of macroerg synthesis and to the reduction of the brain macroerg content. Prophylactic administration of the derivatives of nicotinic acid and GABA markedly stimulated oxidative phosphorylation making it return to the initial level. Mebicar and meprobamate were less powerful. Chlorodiazepoxide aggravated stressful effects on tissue respiration and oxidative phosphorylation. It has been demonstrated that energy metabolism of the brain may return to normal at the expense of stimulation of oxidative phosphorylation.

Animals↗
PubMed1982

Hemoperfusion in acute intoxication. Clinical experience with 48 cases.

Hemoperfusion was performed on 58 occasions to treat 48 patients with severe intoxication, of which 23 had taken on overdose of barbiturate or meprobamate. With one exception they all showed remarkable improvement during the treatment. In addition in many other intoxications patients greatly benefited from hemoperfusion, as with salicylate, paracetamol, quinidine, propranolol and mushroom intoxications. Hemoperfusion was of doubtful value or ineffective in intoxications due to tricyclic antidepressants, phenothiazine, digoxin and methanol. Four of the patients (7%) died. More side effects are seen during hemoperfusion than during hemodialysis. The disposable supplies of hemoperfusion are more costly than those for hemodialysis. Therefore if both kinds of treatment are equally effective, one has to prefer hemodialysis. Unfortunately intoxications exist, which do not respond to either hemoperfusion or hemodialysis.

Adult↗
PubMed1981

[Experimental study of the "'rebound syndrome" following discontinuation of prolonged phenazepam administration and possibilities for preventing it].

Phenazepam given to rats in a daily dose of 2 mg/kg intraperitoneally for a long (30 days) time ceased to produce the sedative effect, and discontinuation of the medication led to development of the so-called "recoil syndrome" characterized by general depression and disturbances of the conditioned-reflex activity. The "recoil syndrome" was distinguished for a selective specificity, since its motor and sensor manifestations were eliminated only by benzodiazepine derivatives (phenazepam, diazepam). Drugs from other chemical slasses (meprobamate, trioxazine, amipazin) did not influence this syndrome.

Animals↗
PubMed1981

[Reduction of catecholamine liberation by drugs. Therapeutic alternative to beta sympathicolysis in coronary disease?].

Plasma catecholamines have been determined in 10 persons with healthy coronary circulation (group A) and in 10 patients with coronary cardiac illness (group B) before and immediately after ergometer loading. The loading dosis amounted on average to 177.5 watts for group A and 80 watts for group B. Under load, the catecholamines rose significantly for group A (p less than 0.01) and highly significantly for group B (p less than 0.001). After 10 days of therapy with a combination preparation (12 mg of diphenhydramine hydrochloride, 100 mg of meprobamate, 5 mg of nicotinic acid = Visano-mini), the catecholamines were again determined for groups A and B before and after loading. The catecholamines were not significantly changed by therapy, neither for group A nor B. Under the therapy, the rise in catecholamines caused by load was distinctly lower than before without therapy, namely significantly lowered for group A (p less than 0.01) and slightly significantly for group B (p less than 0.02). Also significantly lowered under therapy in terms of percentage was the catecholamine rise caused by the load, namely by 27% against 75% for group A, by 35% against 89% for group B. As the first results show, Visano-mini seems to constitute an interesting catecholamine inhibiting combination of substances. Whether this might possibly lead to a therapeutic alternative to the betasympathicolysis will have to be determined on the basis of further investigations.

Adult↗
PubMed1997

Selectivity in the generalization profile in baboons trained to discriminate lorazepam: benzodiazepines, barbiturates and other sedative/anxiolytics.

The discriminative stimulus effects of benzodiazepines often have been indistinguishable from those of barbiturates or other sedative/anxiolytics. However, baboons and rats trained to discriminate lorazepam did not reliably generalize to pentobarbital in previous studies, although animals comparably trained to discriminate pentobarbital reliably generalized to lorazepam. The present study investigated the generalization profile for a variety of anxiolytic, sedative and other drugs in baboons trained to discriminate oral lorazepam (1.8 mg/kg). Triazolam, alprazolam, diazepam, midazolam, bromazepam, temazepam and nordiazepam occasioned >80% of total responses on the lorazepam-paired lever, in that order of potency, 60 min after oral dosing; chlordiazepoxide did so in three of five baboons. However, barbiturates (amobarbital, hexobarbital, methohexital, pentobarbital, phenobarbital, secobarbital) and methypryIon occasioned lorazepam-appropriate responding in only one or two baboons. Testing barbiturates at different pretreatment times (amobarbital, hexobarbital, pentobarbital or secobarbital) or by an i.m. route of administration (methohexital, pentobarbital) did not produce an increase in generalization. Neither other classic sedatives/anxiolytics (chloral hydrate, clomethiazole, ethanol, methaqualone, meprobamate, triclofos), nor anticonvulsants (phenytoin, valproic acid), nor drugs from other pharmacological classes shared discriminative-stimulus effects with lorazepam. These results, together with those from previous studies in which lorazepam or another benzodiazepine served as the training stimulus, indicate that lorazepam training results in a more selective generalization profile with respect to sedative/anxiolytic drugs than does training with other benzodiazepines.

Animals↗
PubMedDate not supplied

Inappropriate drug prescribing in home-dwelling, elderly patients: a population-based survey.

BACKGROUND: In 1997, a US expert panel developed explicit criteria on potentially inappropriate drugs for the general elderly population. OBJECTIVE: To investigate the proportion of inappropriate medications among home-dwelling, elderly patients in Helsinki, Finland, between November 1, 1998, and March 31, 1999. METHODS: A cross-sectional mail survey was sent to a random sample of 3921 elderly urban residents aged 75, 80, 85, 90, and 95 years. Of these, 3219 were home dwellers. MAIN OUTCOMES MEASURES: Prevalence of potentially inappropriate drugs and prevalence of drugs considered inappropriate related to 15 common medical conditions according to recommendations given by the expert panel in 1997. RESULTS: The response rate was 78%. Of the respondents, 12.5%, 1.3%, and 0.2% were taking at least 1, 2, or 3 inappropriate drugs, respectively. The most prevalent inappropriate drugs were dipyridamole (3.6%), long-acting benzodiazepines (2.6%), amitriptyline hydrochloride (1.6%), ergot mesyloids (1.6%), muscle relaxants (1.2%), and meprobamate (1.1%). Use of medications considered inappropriate with certain medical conditions was higher: 27.2% of patients with chronic obstructive pulmonary disease were taking beta-blockers and 19.3% used sedatives. Of diabetic individuals taking oral hypoglycemics or insulin, 32.5% were taking a concomitant beta-blocker. Of those with a peripheral vascular disease, 37.9% were taking beta-blockers. However, two thirds of all these patient groups had concomitant coronary heart disease. CONCLUSIONS: Compared with previous surveys, the use of inappropriate medications in our home-dwelling, elderly population is conspicuously low. In contrast, use of certain drugs considered inappropriate with different medical conditions was relatively high. However, the inappropriateness of the latter treatments may be questioned in individual patients.

Age Factors↗
PubMed1989

Cholecystokinin tetrapeptide induces panic-like attacks in healthy volunteers. Preliminary findings.

A total of 31 intravenous injections of the tetrapeptide cholecystokinin (30-33) were carried out in ten healthy subjects. In seven subjects, cholecystokinin-4 provoked a short-lasting (one to four minutes) panic-like attack (an intense unexplainable fear) at doses between 20 and 100 micrograms. In the other three subjects, doses of 80 to 100 micrograms induced severe anxiety, but no panic-like attack. All subjects experienced severe gastrointestinal symptoms. Pretreatment with lorazepam, but not with meprobamate or naloxone, prevented the psychic effects of cholecystokinin-4 in subjects who had experienced a panic-like attack with the same dose of this peptide. Following the peptide injection, levels of plasma free catecholamines, lactate, and glucose were unchanged, whereas levels of plasma cortisol and prolactin were increased. The intravenous injection of the sulfated cholecystokinin octapeptide (26-33) in two subjects (doses of 35 and 40 micrograms, respectively) produced severe gastrointestinal symptoms, but failed to induce any anxiety or panic-like attacks. These preliminary findings suggest that cholecystokinin-4 may have a panic-inducing effect. It remains to be established if this peptide exerts this effect via a direct activation of central cholecystokinin receptors.

Adult↗
PubMed2000

Drugs for nocturnal enuresis in children (other than desmopressin and tricyclics).

BACKGROUND: Enuresis (bedwetting) is a socially unacceptable and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great. OBJECTIVES: To assess the effects of drugs other than desmopressin and tricyclics on nocturnal enuresis in children, and to compare them with other interventions. SEARCH STRATEGY: The following electronic databases were searched: MEDLINE to June 1997; AMED; ASSIA; BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974 to June 1997); PsycLIT and SIGLE. Organisations, manufacturers, researchers and health professionals concerned with enuresis were contacted for information. The reference sections of obtained studies were also checked for further trials. Date of the most recent search: July 1997. SELECTION CRITERIA: All randomised trials of drugs (excluding desmopressin or tricyclics) for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive drugs compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were provided. Trials focused solely on daytime wetting were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data. MAIN RESULTS: None of the drugs (phenmetrazine, amphetamine sulphate/ephedrine + atropine, furosemide (sic) or chlorprotixine) were better than placebo during treatment. The numbers were too small to draw reliable conclusions, and none are used in current practice in the UK. Imipramine (a tricyclic) was better than each of the three drugs with which it was compared (meprobamate, ephedrine sulphate and furosemide) even though the numbers were small. Alarm treatment was better than drugs in one small trial. REVIEWER'S CONCLUSIONS: There was not enough evidence to suggest that the included drugs reduced bedwetting. There was limited evidence to suggest that imipramine and alarms were better, and in other reviews, desmopressin, tricyclics and alarm interventions have tentatively been shown to be effective.

Child↗
PubMed1976

Patterns and problems of drug consumption in a developing country.

Delayed and sometimes total lack of communications, lower standards of medical care, low physician: population ratio, absence of monitoring systems affect all phases of drug consumption in developing countries--from procedures for introducing a new drug to its marketing on a broad scale, and ultimate decline. The number of prescriptions and the choice of drug are determined only partly by physicians. Such other factors as medicaments furnished by the government either free or at a small charge, the type of health service, accessibility to paramedical and nonmedical advice, as well as hard-sell marketing practices, often through the mass media, tend to set the pattern of drug usage. The practice of drug storming in "home pharmacies", a phenomenon surveyed by the author, is described and the reasons for it analyzed. In general, the categories of drugs (e.g., antibiotics, cardiovascular, analgesics) consumed are the same in the rest of Europe, the United States, and Latin America. Among the minor tranquilizers, the consumption of meprobamate has risen by about a third, chlordiazepoxide markedly, while phenobarbital consumption has remained about the same from 1969 to 1973. This is said to illustrate the pattern of an upward curve in consumption of a new drug, and the displacement of an old one. The overall rise of these drugs during this period was 72.1% in Hungary. Similar surveys are reported for oral hypoglycemic and antiarrhythmic drugs. Of hypotensive drugs, rauwolfia usage has declined and methyldopa has increased by over 200%.

Anti-Arrhythmia Agents↗
PubMed1981

Spectrophotometric determination of dimenhydrinate with Reinecke salt.

A convenient spectrophotometric method was developed for the determination of dimenhydrinate in bulk drug and dosage forms and in 1:1 combinations with aspirin, acetaminophen, meprobamate, phenylephrine, and tolbutamide. The method consisted of reacting dimenhydrinate with reinecke salt in an acidic medium at 27 +/- 2 degrees. The purple precipitate was filtered and dissolved in acetone, and the maximum color absorption attained in 15 min was measured at 540 nm. Evidence is provided to establish the optimal experimental parameters. The stoichiometric balance of the precipitate was determined. Reasonably ideal adherence of the color absorption pattern to the Beer-Lambert law permitted microdetermination of dimenhydrinate in pure form, commercial formulations, laboratory-made combinations, and recovery experiments with good accuracy and repeatability. No interference was observed with any of the drugs or tablet adjuvants.

Dimenhydrinate↗
PubMed1995

The road to tranquility: the search for selective anti-anxiety agents.

The earliest treatments of anxiety included cathartics and emetics, which were used to remove the excess of black bile (hence our word melancholia) thought to be responsible for the patient's demeanor. By the 1700s, physicians were prescribing drugs that are more selective for the CNS, chiefly opium and strengthening tonics. In the 1860s, cardioactive drugs such as atropine, aconite, and digitalis were assumed to counteract anxiety because it could be associated with tachycardia and/or melancholia. A little later, the emergence of laboratory animal models, culminating in the conditioned avoidance response, and also Freudian psychiatry, permitted the evolution of new definitions of anxiety, as well as the introduction of sedative agents such as KBr, chloral hydrate, and barbiturates for its treatment. The first somewhat selective anxiolytics, reserpine, meprobamate, and chlorpromazine, appeared in the early 1950s, while in 1959 the benzodiazepines were the first to prove more selective than all the others in a systematic battery of screening tests.

Animals↗
PubMed1980

Psychotropic drug metabolism in fetal alcohol syndrome.

Simultaneous intake of ethanol with chlorpromazine (thorazine), an antipsychotic drug, leads to about 60% decrease in the chlorpromazine removal from the rat blood. Studies with liver homogenates showed that ethanol inhibits the metabolism of this drug by about 50%. The inhibitory effect of ethanol on the metabolism of chlorpromazine can be largely abolished by pyrazole (2 mM) preincubation. Prolonged maternal ethanol consumption during pregnancy and lactation leads to a decrease in chlorpromazine metabolism in the fetal (30%), neonatal (46%) and maternal livers. Prolonged maternal ethanol intake also leads to an increase in the (UDPG)/(UDPGA) ratio in the suckling neonatal liver and the maternal liver. Simultaneous acute administration of ethanol (2g/kg) with psychotropic drugs such as chlordiazepoxide (librium), diazepam (valium), chlorpromazine (thorazine) or meprobamate (equanil) to pregnant or non-pregnant rats led to a decrease in the blood alcohol clearance rates. In another group of nonpsychotropic drugs tested, tolbutamide (orinase) produced the most pronounced (47%) decrease in blood alcohol clearance rates. This decrease was found to be accompanied by the inhibition of hepatic alcohol dehydrogenase.

Alcohol Oxidoreductases↗
PubMed1982

Prediction of the efficacy of hemoperfusion and hemodialysis in severe poisoning.

The pharmacokinetics of nine drugs were studied in 13 severely intoxicated patients treated with combined hemoperfusion-hemodialysis. Five drugs (phenobarbital, methylphenobarbital, amobarbital, meprobamate, thallium) showed one-compartment kinetics. For two drugs (secobarbital, methaqualone) however a two-compartment model had to be accepted. For the former group a one-compartment linear model can be used to predict the efficacy of treatment and to calculate the optimal duration of treatment.

Hemoperfusion↗
PubMed1982

Behavioural teratology: post-natal consequences of drug exposure in utero.

The effects of pre-natal exposure to drugs that subsequently affect the post-natal behaviour without apparently causing noticeable brain damage forms the subject of behavioural teratology. This review summarizes the experimental studies of several investigators who showed that pre-natal administration of such psychotropic drugs as meprobamate, isocarboxazid and reserpine reduced the maze-learning ability of the mature offspring. A more detailed survey of the effects of D-amphetamine and diazepam is then given. Both drugs were not foetotoxic and only caused appreciable changes in locomotor activity of the offspring at least 14 days after birth. With the amphetamine treated rats, these changes were biphasic (elevated at 15 days and reduced at 21 days) whereas the diazepam treated animals showed a reduction in locomotor activity for at least 21 days after birth. The results of our own studies, and those of others, do not enable a correlation to be made between the effects of the various drugs on the development of specific central neurotransmitters and the behavioural deficits noticed. The review concludes with an outline proposal for screening drugs for their potential as behavioural teratogens. The possible mechanisms whereby behavioural teratogens may cause subtle changes in the maturation of the brain are also outlined.

Amphetamines↗
PubMed1978

A micromethod for the isolation of drugs from blood using amberlite XAD-2.

The extraction of drugs from small blood samples (1 ml or less) for subsequent quantitative determination is described. Isolation was carried out by adsorption of the drugs to Amberlite XAD-2 resin utilizing a batch procedure that enabled the simultaneous extraction of up to 200 samples in approx. 5 hours. A new desorption technique yielded extracts of high purity that could be used directly for gas chromatographic or radioimmunological determinations, even if hemolyzed or putrid blood was to be examined. The following 26 substances were quantitated after addition to postmortem blood speciments at concentrations of 1-10 microgram/ml: tilidine, diphenhydramine, dibenzepine, imipramine, chlorpromazine, amphetamine, pentazocine, phenacetin, methaqualone, meprobamate, parathion, diazepam, digoxin, beta-methyldigoxin, carbromal, glutethimide, amobarbital, pentobarbital, cyclobarbital, phenobarbital, diphenylhydantoin, carbutamide, tolbutamide, glycodiazin, tolazamide and chlorpropamide. Thereby recoveries of 60-100% could be achieved. The reproducibility of the procedure was satisfactory as demonstrated by coefficients of variation of 3.7-8%.

Humans↗
PubMed1988

The influence of psychotropic drugs on the ultrasonic calling of mouse pups.

The influence of a range of commonly used psychotherapeutic drugs on the ultrasonic calling of mouse pups was assessed. The major tranquilizers chlorpromazine and haloperidol were without effect. Whereas tranylcypromine and imipramine were also inactive, amitriptyline suppressed the rate of calling. Some anxiolytic compounds such as meprobamate and amobarbital were without influence, although others such as diazepam, chlordiazepoxide and ipsapirone decreased the number of calls. The influence of these drugs on body temperature was measured, as it is known to markedly influence the rate of ultrasonic calling. Although six out of ten drugs decreased body temperature, there was no evidence that this was related to the rate of ultrasonic calling. The possibility that the recording of ultrasonic calls could be used to screen for psychotropic activity is discussed.

Animals↗
PubMed1978

Isolation of drugs from blood by column chromatography on Amberlite XAD-2.

An investigation was carried out on the isolation of 28 drugs from blood by column chromatography on Amberlite XAD-2. The following substances were added to postmortem blood specimens at concentrations generally of 1--10 microgram/ml: barbital, heptabarbital, hexobarbital, pentobarbital, phenobarbital, phenylbutazone, monocrotophos, amidopyrine, carbromal, diazepam, meprobamate, methaqualone, nitrazepam, phenazetin, chlorpromazine, dibenzepin, diphenhydramine, haloperidol, imipramine, mescaline, methadone, morphine, pentazocine, pethidine, tilidine, triflupromazine, verapamil, N-propylajmalinium bitartrate. The samples were purified by column chromatography on Amberlite XAD-2 and simple solvent extraction and subsequently quantitated by gas chromatography. By systematic variation of the conditions for adsorption of the drugs and desorption from the resin, revoveries of more than 80% after XAD-2 column chromatography could be achieved for most drugs. Thereby it was demonstrated, that in cases of fatal poisoning or emergencies this procedure is a valuable tool for forensic and clinical toxicologists who have to find out the toxic agent by chemical analysis of the blood.

Chromatography, Gas↗
PubMed1981

Anxiolytics antagonize yohimbine's discriminative stimulus properties.

Male Sprague-Dawley rats were trained to discriminate 3.2 mg/kg yohimbine HCl from saline in a two-lever operant procedure. Generalization tests indicated that piperoxane, another alpha 2-adrenergic blocker with anxiogenic properties in humans, produces yohimbine-like discriminati-effects.. In contrast to yohimbine and piperoxane, many other agents were discriminated as vehicle, including corynanthine, raubasine, phentolamine, prazosin, WB-4101, mianserin, tolazoline, and mezilamine. Diazepam caused a dose-related antagonism of yohimbine's stimulus properties. A partial antagonism of yohimbine cueing was also obtained with meprobamate, phenobarbital, chlordiazepoxide, and clonazepam. These results suggest that yohimbine discrimination in rats may be a useful model for detecting agents with anxiolytic activity.

Animals↗