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Biomedical subjects

C A Naranjo

Publications and source records attributed to C A Naranjo.

At least 73 records · Page 4Linked to original sources
PubMed1989

Kinetic and dynamic interactions of oral viqualine and ethanol in man.

We have studied the interaction of viqualine, a 5-hydroxytryptamine (5-HT) uptake inhibitor, with ethanol in 16 healthy men aged 20 to 34 years. The subjects were randomly assigned to receive ethanol dosed to maintain blood alcohol concentrations of 17-22 mmol.l-1 (n = 8) or orange juice (n = 8) on each of two test days one week apart and preceded, in random order, by 3 days of viqualine 75 mg bd or placebo. Ethanol had no effect on steady-state viqualine concentrations or the inhibition of 5-HT uptake. Viqualine did not affect acetaldehyde concentrations or cause an aversive alcohol-sensitizing reaction. The deleterious effects of ethanol on word recall, manual tracking, body sway, and self-ratings of intoxication, sedation, and performance were not modified by the presence of viqualine. Within each beverage group performances and self-ratings on viqualine and placebo days were not different. The first dose of viqualine was associated with transient nausea. Viqualine and ethanol do not interact kinetically or dynamically on the variables examined in this study.

Acetaldehyde↗
PubMed1989

Differential effects of viqualine on alcohol intake and other consummatory behaviors.

Viqualine, a serotonin releaser and uptake inhibitor, was studied for its effects on consummatory behaviors (intake of ethanol and nonalcoholic beverages, cigarette smoking, and changes in body weight) in 29 men who were early-stage problem drinkers between 21 to 55 years of age. Subjects were randomly assigned to receive a placebo and either 100 mg/day viqualine (n = 15) or 200 mg/day viqualine (n = 14) orally in a double-blind crossover study. Viqualine administration and ethanol intake were assessed by self-reports and by measurement of drug and ethanol concentrations in body fluids. Compared with placebo, 100 mg/day viqualine did not decrease ethanol intake. However, 200 mg/day viqualine significantly decreased the total number of drinks consumed in a 14-day period (F1,12 = 5.3; p less than 0.05). An increase in the number of abstinent days was significant only for those subjects who received the placebo first (F1,6 = 11.3, p less than 0.02). Subjects reported a decreased interest in and decreased desire for alcohol during viqualine treatment. Patterns of response varied, but 64% of the subjects decreased the number of alcoholic drinks consumed and/or increased the number of days of abstinence by at least 25% during treatment with 200 mg/day viqualine compared with placebo treatment. Neither dose of viqualine had an effect on cigarette smoking or on consumption of nonalcoholic beverages, but subjects showed significant decreases in body weight with both doses. These findings indicate that viqualine both attenuates ethanol intake and reduces body weight in human beings.

Adult↗
PubMed1989

Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar).

A shortened 10-item scale for clinical quantitation of the severity of the alcohol withdrawal syndrome has been developed. This scale offers an increase in efficiency while at the same time retaining clinical usefulness, validity and reliability. It can be incorporated into the usual clinical care of patients undergoing alcohol withdrawal and into clinical drug trials of alcohol withdrawal.

Alcohol Withdrawal Delirium↗
PubMed1988

Limitations in the measurement of urine ethanol in clinical trials to monitor ethanol consumption.

Self-report of daily alcohol consumption has been used as the dependent variable in clinical trials to assess the effects of two serotonin uptake inhibitory drugs, zimelidine and citalopram. The validity of the dairy data was established by correlating concentration of ethanol in daily urine samples with number of reported standard alcoholic drinks (r = 0.62 for the 934 subject-days in the zimelidine study; r = 0.54 for the 3,103 subject-days in the citalopram study, both p less than 0.0001). The effects of factors other than inaccurate reporting, such as the range of values for reported daily drinks and subjects' drinking patterns, on the correlation coefficients for all subject-days and for individual subjects in the citalopram study are discussed. Sampling 50% or fewer of the 84 days of the citalopram study for each subject is economically advantageous and did not significantly change the values of the correlation coefficients or the rank positions of subjects but did increase the 95% confidence intervals for the correlation coefficients, indicating less certainty about the actual correlation coefficients and, therefore, the accuracy of a subject's self-report. The ability of urine ethanol concentration to validate objectively diaries of alcohol consumption is limited by factors that must be considered but are likely to be out of the investigator's control.

Adult↗
PubMed1988

Protracted tinnitus after discontinuation of long-term therapeutic use of benzodiazepines.

The presence of protracted tinnitus after discontinuation of long-term therapeutic doses of diazepam (less than or equal to 30 mg/day) is described in three patients. In one of these patients, the association of the tinnitus appearance with the drug discontinuation was documented in a double-blind, randomized, crossover single case study. Objective confirmation of drug use or of abstinence was performed by obtaining plasma benzodiazepine concentrations. The findings provide further documentation that sensory disturbances of short- and long-term duration are among the most distinctive clinical features of the benzodiazepine withdrawal syndrome.

Adult↗
PubMed1987

Nifedipine delays the acquisition of tolerance to ethanol.

Rats were trained to remain on a motor-driven belt until they reached a criterion of not exceeding 1% error (1.2 s off the belt) in a 2 min trial. Upon completion of training, animals were treated with nifedipine and/or ethanol and were tested for degree of impairment after an i.p. injection of 2 g/kg ethanol solution on test days. Chronic nifedipine treatment enhances the acute ethanol effects on motor impairment and delays the acquisition of tolerance to ethanol. Results suggest modification of brain calcium channel activities could delay the development of tolerance to ethanol and may prevent ethanol-induced organic brain damage.

Animals↗
PubMed1987

Drug deprivation and reinforcement by diazepam in a dependent population.

Individuals who were using therapeutic doses (approximately 15 mg diazepam or its equivalent daily) of a benzodiazepine persistently and wished to attempt to stop were recruited into a study offering a medically supported outpatient behavioral treatment with a goal of abstinence. All subjects received the same behavioral treatment that emphasized the development of strategies for coping with abstinence and alternatives to benzodiazepines as a coping mechanism. The goal of abstinence was to be achieved within approximately 8 weeks by means of gradual tapering of the daily dose. Some subjects (Group D, n = 23) were randomly assigned to a condition in which their dose was to be tapered on a regime of active diazepam. Others (Group P, n = 19) were switched to placebo at the first treatment session and "tapered" from this pharmacologically inert substitute for diazepam. Supplies of tablets of each preparation were provided by the experimenters, and subjects were specifically requested to use only those tablets. The principal dependent variable was "supplementation", or use of a benzodiazepine other than that specifically authorized by the therapist. Supplementation was detected by measures of plasma benzodiazepine levels as compared to levels predicted if there had been strict compliance with the therapeutic regime. These comparisons were made by two expert judges who were blind to the subjects' experimental assignment. Self-report of supplementation was also obtained. Plasma level determinations indicated a significantly greater frequency of supplementation (84% versus 33% of subjects) for subjects in Group P.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Increase in the brain regional depolarization-dependent Ca2+ uptake in rats preferring ethanol.

The depolarization-dependent Ca2+ uptake system has been suggested to be involved in the release of transmitter and synaptic facilitation. It can be employed as an effective probe to study neurotransmission. Although ethanol has been shown to inhibit or facilitate neurotransmission very little is known about the intrinsic activity of neurotransmission in ethanol-preferring rats. Using the depolarization-dependent Ca2+ uptake system, we demonstrated that synaptic neurotransmission is more active in animals with moderate and high preference for ethanol. Results suggest that there are intrinsic differences in the brain regional neurotransmission among rats showing different degrees of preference for ethanol.

Alcohol Drinking↗
PubMed1987

The serotonin uptake inhibitor citalopram attenuates ethanol intake.

No effective drug for decreasing ethanol intake is available for clinical use. Our previous studies showed that zimeldine decreased ethanol intake in rats and nondepressed alcohol abusers. However, zimeldine was withdrawn from the market because of serious toxicity. We tested citalopram, a selective serotonin uptake inhibitor, in 39 male nondepressed early-stage problem drinkers (aged 19 to 61 years). Subjects were randomly allocated to receive either citalopram, 20 (n = 20) or 40 (n = 19) mg/day orally, or placebo in a double-blind, crossover trial. Citalopram administration and ethanol intake were assessed by self-report and objectively. Citalopram, 20 mg/day, did not show an effect. However, citalopram, 40 mg/day, decreased the number of drinks consumed (F1,17 = 5.27; P less than 0.05) and increased the number of abstinent days (F1,17 = 13.18; P less than 0.005). The effect is probably through modulation of the neurobiologic mechanisms regulating ethanol intake. Our results suggest a new pharmacologic approach to decrease ethanol intake.

Adult↗
PubMed1987

Do serotonin uptake inhibitors decrease smoking? Observations in a group of heavy drinkers.

Serotonin uptake inhibitors have been reported to alter several consummatory and drug self-administration behaviors in rats. These observations suggest important therapeutic applications in humans. While evaluating zimelidine and citalopram effects on ethanol intake, we also assessed smoking behavior. Five male heavy drinkers smoking 29.7 +/- 9.0 (mean +/- SD) cigarettes a day were randomly allocated to receive zimelidine (200 mg/day orally) or placebo in a double-blind crossover study. Another 17 male heavy drinkers smoking 21.1 +/- 14.3 (mean +/- SD) cigarettes a day were randomly allocated to receive citalopram (20 or 40 mg/day orally) or placebo in a double-blind crossover study. In both studies, subjects were not trying to modify their smoking or drinking and received no advice or other treatment to do so. Zimelidine had no effects on the number of cigarettes smoked (F1,4 = 1.80, not significant (NS]. Neither citalopram dose had an effect on smoking (citalopram 20 mg: F1,8 = 0.06, NS; citalopram 40 mg: F1,7 = 0.68, NS). Because intrasubject variation is small, this trial was of sufficient size to exclude with 99.99% confidence the possibility that these drugs decrease smoking behavior by 50%. Since serotonin uptake inhibitors can attenuate ethanol intake in humans, these drugs may have differential effects on consummatory behaviors.

Adult↗
PubMed1986

Withdrawal reaction after long-term therapeutic use of benzodiazepines.

We conducted a double-blind, placebo-controlled trail in which 40 patients who had undergone long-term therapy with benzodiazepines were switched to placebo or to diazepam in a dose approximately equivalent to their usual dose of the benzodiazepine; the dose of diazepam was then tapered during an eight-week period. Patients were assessed clinically and psychologically and had weekly sessions of behavioral therapy. The subjects who received placebo had more symptoms, assessed their symptoms as more severe, and stopped taking the study drug at a higher rate than those receiving the tapering doses of diazepam. The subjects in the placebo group also had symptoms shortly after being switched to placebo, whereas those in the diazepam group had symptoms much later. Some withdrawal symptoms were distinct from those of anxiety (e.g., tinnitus, involuntary movement, and perceptual changes). Withdrawal symptoms occurred earlier in patients who had received short-acting benzodiazepines than in those who had received long-acting benzodiazepines. Symptoms gradually disappeared over a four-week period in both the placebo and the diazepam groups. Serial determination of plasma benzodiazepine concentrations was a useful way to assess compliance, treatment outcome, and relapse during withdrawal. We conclude that a clinically important, mild, but distinct withdrawal syndrome occurs after discontinuation of long-term therapeutic use of benzodiazepines.

Adolescent↗
PubMed1986

Clinical assessment and pharmacotherapy of the alcohol withdrawal syndrome.

All patients in alcohol withdrawal should have a full assessment for detecting medical complications. The Clinical Institute Withdrawal Assessment for Alcohol (CIWA-A) scale permits a quantitative assessment for following the clinical course and therapeutic response in patients in withdrawal. Most patients with mild withdrawal symptoms do not require hospitalization and respond to non-pharmacologic supportive care. Early initiation of treatment with supportive nursing care and, if necessary, benzodiazepines usually will prevent progression to serious withdrawal reactions and provide the patient with sufficient symptomatic relief. Pharmacotherapy can be considerably simplified by using the loading dose technique, i.e., giving diazepam every 1-2 hr initially until the patient shows signs of clinical improvement and/or mild sedation. If long half-life drugs (e.g., diazepam) are used, further therapy is rarely needed and complications are prevented. Short-acting benzodiazepines can also be given in a similar fashion in the milder clinical syndrome. Phenytoin should only be given to patients with a preexisting seizure disorder. Phenothiazines, barbiturates, paraldehyde, and antihistamines have no role in the treatment of withdrawal because of their toxicity or lack of efficacy. Haloperidol is effective in the control of hallucinations in patients also treated with a benzodiazepine. The treatment of alcoholic intoxication and withdrawal is only the first step toward full rehabilitation.

Adrenergic beta-Antagonists↗
PubMed1986

Chronic ethanol inhibits rat hippocampal "stimulus-secretion" coupling mechanism for 5-hydroxytryptamine in vitro.

Effects of ethanol on serotonergic neurotransmission were investigated in crude mitochondrial fraction (P2 fraction) from rat brain hippocampus and hypothalamus. The [14C]5-HT preloaded P2 fraction was exposed to 45 mM KCl to induce 5-hydroxytryptamine release in vitro. Ethanol in vitro did not produce any significant inhibition of [14C]5-HT release until its concentration was greater than 100 mM. The K+-evoked 45Ca uptake of hippocampal P2 fraction was unaffected by 100 mM. However, 200 mM ethanol inhibited approximately 63% of K+-evoked 45Ca uptake. Chronic ethanol (10 g/kg/day) for 6 days inhibited [14C]5-HT release from hippocampus whereas it did not affect [14C]5-HT release from hypothalamus. Results indicate that chronic ethanol treatment may decrease serotonergic neurotransmission in selective brain regions. The reduction in 5-hydroxytryptamine release was the result of inhibition in "stimulus-secretion" coupling mechanism.

Alcoholism↗
PubMed1986

Modulation of ethanol intake by serotonin uptake inhibitors.

The most commonly prescribed agents for decreasing ethanol intake are alcohol-sensitizing drugs; however, their efficacy is unproven, they are associated with toxicity, and there are several contraindications for use. A program to identify and test new drugs to decrease ethanol intake has focused on drugs that enhance central serotonergic neurotransmission and consistently attenuate ethanol consumption. Animal studies have shown consistent findings with direct and indirect serotonin (5-HT) agonists. Ethanol intake decreased after the administration of 5-HT precursors, 5-HT uptake inhibitors, intracerebral 5-HT, and postsynaptic 5-HT agonists; in contrast, destruction of serotonin-containing neurons with 5,6- or 5,7-dihydroxytryptamine increased ethanol intake. Administration of zimelidine (200 mg/day p.o.) to 16 healthy alcohol abusers was associated with a significant increase in number of abstinent days and a decrease in number of drinks consumed. Approximately 50% of the subjects were responders, 35% were partial responders, and 10%-15% were nonresponders. In a recent double-blind crossover study, citalopram, an even more selective serotonin uptake inhibitor, produced similar results. Because serotonin uptake inhibitors acted rapidly and subjects were not clinically depressed, this action is distinct from antidepressant effects. These drugs most likely interfere with the neurobiologic mechanisms regulating ethanol intake and provide an innovative approach for modulating the use of alcohol in problem drinkers.

Acetaldehyde↗