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PubMed1976

Influence of secobarbital and chlorpromazine on precentral neuron activity during attentive behavior in monkeys.

Precentral motor cortex neurons were studied under non-drug and drug conditions in three trained monkeys during the performance of a go-no go visual "attention" task. The two drugs studied, secobarbital and chlorpromazine, produced differing patterns of effect on components of the motor sequence involved in reaction time. The following components were considered: The SF interval or the period from stimulus onset to change in neuronal firing; the FR interval, which is the period from change in firing to the beginning of the task response; and MT or movement time, which is the time necessary to complete the response. Secobarbital produced an increase of 80% in SF and a relatively small average change in FR although there was considerable variability in the latter. MT was decreased in most secobarbital experiments. Anatomical factors relating to the FR variability were considered, and the MT decrease was discussed in terms of possible excitatory effects of the drug. Chlorpromazine produced small increases in SF, FR and MT, alternating with periods of complete abolition of performance. The results were discussed in terms of theories of attention deficit following administration of secobarbital and chlorpromazine.

Action Potentials↗
PubMed1989

Effect of d-amphetamine, secobarbital, and marijuana on choice behavior: social versus nonsocial options.

The effects of oral d-amphetamine and secobarbital and smoked marijuana on human social conversation and preference for socializing were studied in three separate experiments. During experimental sessions, active drug or placebo was administered using an acute or divided dosing procedure. Subjects who received drug then engaged in a discrete-trial choice procedure in which they made a series of mutually exclusive choices between a social (talking with their nondrugged partner) and nonsocial (sitting quietly alone) option. Lapel microphones and voice operated relays measured seconds of speech. Subjects engaged in greater amounts of conversation and chose the social option more frequently following acute dosing of d-amphetamine and secobarbital compared with placebo. Acute administration of marijuana did not significantly affect social speech or choice behavior, producing slight decreases in both measures. Acute dosing of all drugs significantly increased subjective drug effect or drug high; however, only secobarbital affected the circular lights task, producing significant performance decrements. The shifts in preference toward the social option observed with d-amphetamine and secobarbital suggest that these drugs increased the reinforcing effects of socializing relative to sitting alone. This may be one mechanism by which psychoactive drugs facilitate social conversation.

Adult↗
PubMed1993

Secobarbital attenuates excitotoxicity but potentiates oxygen-glucose deprivation neuronal injury in cortical cell culture.

We examined the effects of secobarbital and other sedative-hypnotic barbiturates on the neuronal death induced by exposure to excitatory amino acids or deprivation of oxygen or glucose in mouse cortical cell cultures. N-Methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate, and kainate toxicities were attenuated in a concentration-dependent fashion by high concentrations of secobarbital or thiopental. Antagonism of NMDA toxicity was not overcome by increasing NMDA concentration and not mimicked by gamma-aminobutyrate. Despite these antiexcitotoxic actions, secobarbital exacerbated the neuronal death induced by deprivation of either glucose alone or oxygen and glucose together; death induced by oxygen deprivation alone was little affected. Thiopental and methohexital also increased oxygen-glucose deprivation injury. A possible explanation for this injury potentiation was provided by the observation that secobarbital enhanced the cellular ATP depletion induced by combined oxygen-glucose deprivation. Deleterious effects on ATP production may counterbalance the protective effects of barbiturates under some conditions.

Adenosine Triphosphate↗
PubMed1983

Effect of secobarbital on theophylline clearance.

Increased clearance of theophylline after the administration of secobarbital was observed in a child receiving phenobarbital. Prior to barbiturate treatment, theophylline clearance was 4.78 ml/kg/min. Beginning 10 days after the institution of secobarbital and phenobarbital therapy, a continually increasing amount of theophylline was required to maintain therapeutic serum concentrations. After 29 days of barbiturate administration, theophylline clearance attained a peak value of 16.1 ml/kg/min, an increase of 337% from the prebarbiturate rate. During this time it was necessary to administer theophylline at a dosage four times above that usually recommended. After secobarbital was discontinued, theophylline clearance returned to 4.53 ml/kg/min. The decrease in theophylline clearance occurred while phenobarbital dosage remained stable. It is apparent that changes in secobarbital dosing were subsequently followed by changes in the clearance of theophylline.

Drug Interactions↗
PubMed1979

Dose-response studies on tolerance to multiple doses of secobarbital and methaqualone in a polydrug abuse population.

Patients from a polydrug abuse treatment program were titrated with either secobarbital or methaqualone, their primary drug of abuse, to a state of mild intoxication, consisting of lateral and vertical nystagmus, ataxia, slurred speech, and drownsiness. The mean dose required to produce each sign was compared to that determined in a similarly treated control group. Tolerance to secobarbital was more easily demonstrated than tolerance to methaqualone, and nystagmus was the least sensitive indicator of patient tolerance. The individual signs were also cumulated into a graded rating scale of central nervous system depression which would be related to the dose administered. Tolerence was easily demonstrated at the higher stages of toxicity for secobarbital in the overall patient population, but tolerance to methaqualone was only unequivocal in the subjects indicating a relatively high frequency of abuse. Tolerance to methaqualone occurred at the lower stages of toxicity, suggesting that there is a difference between tolerance to secobarbital and tolerance to methaqualone. There was no indication that patients who also abuse alcohol are more tolerant than their patient counterparts. The patients who also had a history of amphetamine abuse, however, were less tolerant than the nonusers of these drugs.

Adolescent↗
PubMed2000

Determination of amobarbital and secobarbital in plasma samples using micellar liquid chromatography.

A new liquid chromatographic procedure for the determination of amobarbital and secobarbital in plasma samples is proposed. The method uses a Spherisorb octadecylsilane ODS-2 C(18) analytical column, a guard column of similar characteristics and 0.04 M CTAB solution buffered at pH 7.5 containing 3% 1-propanol as micellar mobile phase. The UV detection was carried out at 250 nm. Butabarbital was used as internal standard. Plasma samples preparation only required adequate dilution with the mobile phase before injection into the chromatographic system. The limits of detection were 0.2 and 0.4 mg/L for amobarbital and secobarbital, respectively. The proposed method allows the determination of amobarbital and secobarbital in plasma at therapeutic levels.

Amobarbital↗
PubMed1975

Effects of marihuana combined with secobarbital.

Twelve male volunteers smoked a marihuana cigarette prepared to deliver 0 or 25 mug/kg tetrahydrocannabinol (THC) 50 min after ingesting a capsule containing either placebo or 150 mg/70 kg sodium secobarbital. Drugs were administered in a double-blind manner, and all treatments were assigned to each subject in a randomized complete block design. Objective and subjective tests designed to measure mental and motor performance indicated that marihuana impaired stability, hand-eye coordination, and mental performance. Secobarbital affected motor performance, manual coordination, and mental performance. In combination, marihuana and secobarbital had an additive effect on subjective responses and impairment in certain psychomotor performance tests.

Adult↗
PubMed1982

An improved high-pressure liquid chromatographic assay for secobarbital in serum.

A high-pressure liquid chromatographic method for the analysis of secobarbital in serum was developed. Secobarbital was extracted from buffered serum (pH 5.5) with a solvent mix of hexane-ether-n-propanol. 5-(4-Methylphenyl)-5-phenylhydantoin was added as an internal standard. Separation of secobarbital and internal standard from serum constituents and other drugs was achieved on a 5-mum C-18 reversed-phase column using an acetonitrile-phosphate buffer (pH 4.4) mobile phase. The eluent was monitored at 195 nm. The sensitivity limit of the assay was approximately 0.02 microgram/ml with 0.5 ml of serum sample. The application of this method to pharmacokinetic studies in pediatric patients was demonstrated.

Child, Preschool↗
PubMed1975

EEG correlates of impaired attention performance under secobarbital and chlorpromazine in the monkey.

The effects of secobarbital and chlropromazine upon behavior in a continuous, rapidly presented successive (go-no go) discrimination ("attention") task were evaluated in six Macaca mulatta monkeys. Simultaneous monitoring of EEG activity from epidural and subcortical electrodes permitted an evaluation of the nature of altered central nervous system events during erroneous performance (errors of omission) on this task. The computer-assisted analysis of pre-stimulus and post-stimulus EEG frequency activity (baseline crossings) suggests that the best measure of attentive behavior from the pre-stimulus EEG is percentage of beta 2 (25-40 cps) activity. No difference could be observed between drugs or among cerebral placements in this regard. This was determined by comparing measures of EEG frequency, pooled for a given test period, with performance from the same test period. On a trail-by-trail basis. however, the beta 2 measure in the pre-stimulus epoch failed to ditinguish correct responses from errors of omission. Separation between correct responses and errors of omission is possible if comparisons are made between the changes in percentage of beta 2 activity in the pre-stimulus vs. post-stimulus occurs with correct positive trials and the smallest change with correct negative trials. For secobarbital, no difference could be detected between correct and incorrect positive trials. For chlorpromazine, however, there was significantly less change in beta 2 for incorrect positive than for correct positive trials. The results were interpreted in terms of the hypothesis that secobarbital produces errors by depression of the general level of activation whereas chlorpromazine acts by reducing the sensory input which is necessary for correct discrimination performance.

Animals↗
PubMed1983

Chronic insomnia: effects of tryptophan, flurazepam, secobarbital, and placebo.

This study compared the effects of l-tryptophan (1 g), secobarbital (100 mg), flurazepam (30 mg), and placebo on sleep in 96 serious insomniacs. Each treatment was given nightly for 7 nights in a separate-group design. Outcome measures were subjective estimates by subjects of a number of sleep parameters during the week of treatment and for 1 week after, and an overall evaluation made by subjects and investigators at the end of the 2 weeks. During the treatment week, flurazepam produced significant improvement on several sleep measures compared to placebo, while tryptophan and secobarbital did not. Flurazepam and secobarbital produced withdrawal symptoms during the post-treatment week, while tryptophan and placebo did not. Sleep latency was not significantly improved by tryptophan during the treatment week, but continued to improve during the post-treatment week, resulting in a significant difference between tryptophan and baseline in week 2.

Adult↗
PubMed1981

Human social conversation: effects of ethanol, secobarbital and chlorpromazine.

Effects of oral ethanol, secobarbital and chlorpromazine on human vocalization were studied in a dyadic social situation using repeated observations within subject pairs. Throat microphones and voice operated relays were used to measure quantitative aspects of vocalization (conversational speech) during daily experimental sessions. Ethanol (1-6 oz of 95-proof) and secobarbital (30-300 mg) produced dose-related increases in vocalization by the subject who received active drug, while vocalization by the partner who received placebo only was not generally altered systematically. Chlorpromazine (25-100 mg) produced dose-related decreases in amount of vocalization by the subject and vocalization by partners tended to decrease as well on days when the subject received active drug. Selected scales from the Addiction Research Center Inventory were administered following social sessions to assess subjective drug effects. No consistent changes on ARCI scales were obtained after ethanol or secobarbital, while chlorpromazine produced dose-related increases on the PCAG scale. Overall, quantitative measures of vocalization in a social context provided a reliable and sensitive indicator of dose-related drug effects.

Adolescent↗
PubMed1985

Effects of acute ethanol intoxication combined with secobarbital abuse on hemostasis.

Male Sprague-Dawley rats were treated with 0.5 ml of 46% ETOH, 2.8 mg/kg of secobarbital or 14.3 mg/kg secobarbital or combinations thereof. Twenty-four hours following treatment, blood clotting data was determined. The data indicated that either ethanol or secobarbital alone is just as detrimental to hemostasis as is the combined abuse of both. Likewise, a lesser concentration of alcohol was just as disruptive on hemostasis as was the greater concentration of ethanol.

Alcoholic Intoxication↗
PubMed1989

Effects of secobarbital on human aggressive and non-aggressive responding.

This study examined the effects of secobarbital on human aggressive responding in a controlled laboratory setting. Sixty minutes prior to experimental sessions, male subjects were administered either placebo or 50, 100 or 200 mg per 70 kg of body weight doses of secobarbital double-blind. During these sessions, subjects could press a button to accumulate points exchangeable for money (non-aggressive response) or press another button ostensibly to subtract points from a fictitious person (aggressive response). Aggressive responding was occasioned by subtracting points from the subject. Subjects were instructed that points were subtracted by another person. Aggressive responding was maintained by contingent presentation of periods free of point subtractions, i.e., provocations. Acute secobarbital administration produced dose-dependent decreases in non-aggressive responding, and increases in aggressive responding.

Aggression↗
PubMed1997

Secobarbital in humans discriminating triazolam under two-response and novel-response procedures.

Humans were trained to discriminate the benzodiazepine triazolam (0.32 mg/70 kg) from placebo under a two-response (drug vs. placebo) drug discrimination procedure. Dose-effect curves for several drugs were then determined in a crossover design using the two-response procedure and a 'novel-response procedure' that provided a novel-appropriate response for drugs unlike triazolam or placebo. Three subjects were tested with triazolam (0.1-0.32 mg/70 kg), the barbiturate secobarbital (56-177 mg/70 kg), and caffeine (320 and 560 mg/70 kg). Triazolam dose dependently increased triazolam-appropriate responding under both procedures and generally did not occasion novel-appropriate responding under the novel-response procedure. Secobarbital substituted for triazolam in the two-response procedure and dose-dependently increased novel-appropriate responding as well as occasioned some triazolam-appropriate responding in the novel-response procedure. Caffeine generally occasioned placebo-appropriate responding under the two-response procedure and a mix of novel- and placebo-appropriate responding under the novel-response procedure. Triazolam and secobarbital produced qualitatively similar self-reported drug effects. These results suggest that the novel-response procedure for human drug discrimination may enhance the pharmacological selectivity of triazolam- and placebo-appropriate responding.

Adult↗
PubMed1990

Alcohol and secobarbital effects as a function of familial alcoholism: acute psychophysiological effects.

Previous research has demonstrated response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism. These response differences are thought to reflect differences in vulnerability to dependence on alcohol. Thus, the role of positive family alcoholism history in increasing risk of addiction to a variety of drug classes might be studied by determining whether FHP subjects show different responses to drug classes other than alcohol. This was done in the present study by determining dose-effect functions for a variety of physiological (heart rate, skin conductance, skin temperature), subjective (analog mood and drug effect, Subjective High Assessment Scale), and psychomotor measures (hand tremor, body sway, Digit Symbol Substitution Test, eye-hand coordination, and numeric recall) in FHP and FHN college-aged males for secobarbital (0, 100, 200 mg by mouth) and ethanol (1 g/kg). FHP and FHN subjects were matched on light-to-moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. At equivalent blood alcohol levels family-history positive subjects reported greater effects of ethanol than did family-history negative subjects on almost all subjective measures. Following the high dose of secobarbital, FHP but not FHN subjects showed elevated subjective effects; these effects were substantially less and were evident in fewer measures than following ethanol. In contrast to effects on the subjective measures, ethanol and secobarbital produced comparable impairment in both groups of subjects for most psychomotor responses. Group differences were not obtained on any physiological measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Alcohol and secobarbital effects as a function of familial alcoholism: extended intoxication and increased withdrawal effects.

Response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism have been demonstrated in previous research and are thought to be related to risk for developing alcoholism. If this is so, the pharmacological breadth of addiction risk conferred by a positive family alcoholism history might be studied by determining whether FHP subjects show different responses than FHN to drug classes other than alcohol. We have previously reported on the acute effects of ethanol as compared with secobarbital in FHP and FHN subjects and found that FHP subjects showed greater sensitivity across a variety of subjective measures than FHN subjects for both drug classes. The data reported here are based on an extended data collection period of 3 to 18 hr postingestion, following completion of the acute laboratory portion of the study. Specifically, in the present study, dose-effect timecourse functions for a variety of physiological (heart rate, blood pressure, and breath alcohol level), subjective (analog mood, drug effect, and withdrawal, Subjective High Assessment Scale (SHAS], and psychomotor measures (Digit Symbol Substitution Test and numeric recall) were examined in FHP and FHN college-aged males for secobarbital (0, 100, 200 mg daily) and ethanol (1 g/kg daily). FHP and FHN subjects were matched on light-to-moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. FHP subjects reported more extended intoxication and greater withdrawal effects following both ethanol and the high dose of secobarbital than did FHN subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1978

A clinical comparison of triazolam with placebo and with secobarbital in insomniac patients.

Seventy-six out-patient insomniacs participated in three different two-night, double-blind crossover trials investigating the hypnotic efficacy andsafety of triazolam. Triazolam 0.5 mg was compared to placebo in one trial conducted K Kay Okawa, MD, and triazolam 0.5 mg was compared to secobarbital 100 mg in trials conducted by K Kay Okawa, MD and George S Allen, MD. The results of the later two studies were combined and the data analyzed jointly. Triazolam 0.5 mg was found to be preferred and to be significantly better than both placebo and secobarbital 100 mg in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to either placebo or secobarbital on the following parameters: how much the medication helped the patients sleep; onset of sleep; duration of sleep; and number of nocturnal awakenings. No differences were observed between treatments in any trial with regard to the patient's feeling of alertness the next morning. The side-effects reported for all treatments did not significantly interfere with the patient's ability to function.

Adult↗
PubMed1978

Secobarbital and information processing.

The Sternberg fixed-set memory-search paradigm was used to assess the relative vulnerability of hypothetical stages of information processing to an oral dose of secobarbital (2.9 mg/kg). D-amphetamine (15 mg, oral dose) was intended to serve as an active placebo. However, since the amphetamine produced a slight, non-significant reduction in choice reaction time (RT), the principal analysis of secobarbital effects was conducted between drug and baseline conditions. Secobarbital showed choice RT by 60 msec. and did not increase errors significantly. The results, as interpreted within Sternberg's model, suggest that input processes, e.g., stimulus preprocessing-encoding, are particularly sensitive to the effects of the barbiturate. There was no evidence of a drug effect on cognitive processes associated with serial comparison, binary decision, or translation-response organization (response selection). In contrast, earlier studies have indicated that another CNS depressant, alcohol, interferes with both speed and accuracy of output processes, viz, the response selection stage.

Adult↗