Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Chlordiazepoxide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMedDate not supplied

Facilitation of avoidance behavior by chlordiazepoxide and chlordiazepoxide-amphetamine combination: effect on performance.

Chlordiazepoxide, 5 mg/kg, given at various stages of training invariably facilitated the shuttle box avoidance of CD-1 mice for a short period of time (100 trials); no after-effects were observed on the following daily session. Amphetamine, 1 mg/kg, usually did not facilitate significantly the responding, but its combination with chlordiazepoxide produced a stronger and more pronounced effect than that of chlordiazepoxide alone. In prolonged (600-trial) sessions the performance of mice declined in the second half of the session; this decline was temporarily reversed by chlordiazepoxide given alone or with amphetamine after the first 300 trials. The results indicate that the facilitation of shuttle-box avoidance behavior by chlordiazepoxide or chlordiazepoxide-amphetamine combination is due to the improvement of performance.

Amphetamine↗
PubMed1984

Assay of chlordiazepoxide and demoxepam in chlordiazepoxide formulations by difference spectrophotometry.

Rapid difference spectrophotometric methods for chlordiazepoxide and demoxepam in chlordiazepoxide formulations are described which overcome the nonspecificity of the official spectrophotometric assays. The procedures are based on the measurement of the difference absorbance at 269 nm of equimolar solutions of chlordiazepoxide at pH 8 and pH 3 and the difference absorbance at 263 nm of equimolar solutions of demoxepam at pH 13 and pH 8. The methods are specific for chlordiazepoxide and demoxepam in the presence of both compounds, 2-amino-5-chlorobenzophenone, certain coformulated drugs, and formulation excipients. Analyses of commercial dosage forms of chlordiazepoxide have shown the presence of demoxepam at concentrations in excess of the pharmacopoeial specifications in some aged samples.

Anti-Anxiety Agents↗
PubMed1986

Facilitation of stimulatory effect of chlordiazepoxide-amphetamine combination by subacute administration of chlordiazepoxide in mice.

Spontaneous locomotor activity was tested in CD-1 mice receiving subacutely (for 4 days) chlordiazepoxide (10 mg/kg) and then treated with d-amphetamine (0.5 or 1 mg/kg) and various doses of chlordiazepoxide (2.5, 5 or 10 mg/kg) separately or in combination. Chlordiazepoxide pretreatment enhanced the stimulatory effect of the chlordiazepoxide-amphetamine combination.

Animals↗
PubMed1990

Chronic treatment with ethanol or chlordiazepoxide alters the metabolism of chlordiazepoxide.

Although chronic ethanol administration in C57BL/6J mice did not cause an induction of ethanol metabolism, it altered the metabolism of chlordiazepoxide (CDP). Significantly lower blood levels of CDP, but higher levels of N-desmethyl CDP (NDCDP), were observed in ethanol-dependent mice compared to pair-fed controls during the first hour after CDP injection. Mice treated chronically with CDP showed significantly lower blood levels of CDP and NDCDP than pair-fed controls after a test dose of CDP. In response to an injection of ethanol, the CDP-dependent mice had lower blood alcohol levels (BAL) than the pair-fed controls, but the rate of fall of BAL was not different in the two groups. Thus, chronic CDP treatment affected the absorption and distribution of ethanol. These results provide a metabolic basis for the manifestations of CDP tolerance and ethanol cross-tolerance that have been reported in CDP-dependent mice.

Animals↗
PubMed1984

Blood concentrations and clinical findings following overdose of chlordiazepoxide alone and chlordiazepoxide plus ethanol.

Blood concentrations and clinical findings in 25 cases of overdose involving chlordiazepoxide (CDZ) alone ("pure") were compared with those in 23 cases of overdose involving ethanol in addition to CDZ ("mixed"). Both groups consisted predominantly of men who were chronic alcoholics. The mean blood CDZ concentrations did not show statistically significant difference between the two groups ("pure," 5 mg/L; "mixed," 6 mg/L). Following "pure" ingestion, patients were usually alert, and the level of consciousness showed no statistically significant correlation with the blood CDZ concentration. In contrast, after "mixed" ingestion patients were usually lethargic, and the level of consciousness correlated significantly with the blood CDZ concentration (P less than 0.05) but not with the blood ethanol concentration. In neither group was coma noted. For both groups the most common physical findings were tachycardia and dysarthria. Nystagmus was much more common following "mixed" ingestion while seizures, hyperreflexia, and hypertension were more frequent after CDZ overdose alone. Most patients were seen only in the emergency room and were discharged. The implications of these findings are discussed.

Adolescent↗
PubMed1985

Behavioral effects of nonbenzodiazepine anxiolytic drugs: a comparison of CGS 9896 and zopiclone with chlordiazepoxide.

Zopiclone and CGS 9896 are two nonbenzodiazepine compounds which have been shown to displace benzodiazepines from their binding sites. The present study compared the behavioral effects of these two compounds in rats with those of chlordiazepoxide. The three drugs produced dose-related increases in punished drinking as did pentobarbital and meprobamate but not PK 9084, which also acts at benzodiazepine binding sites, or buspirone. Rates of lever pressing suppressed by punishment were also increased by chlordiazepoxide and zopiclone. CGS 9896 exerted a similar although less marked effect. Lever pressing maintained by a differential reinforcement of low rate 18-sec schedule of milk presentation was increased by low doses of chlordiazepoxide and zopiclone and decreased by higher doses leading to dose-related reductions in numbers of reinforcers obtained. CGS 9896 also reduced number of reinforcers but without affecting rate of responding. In rats trained to discriminate a dose of chlordiazepoxide from saline, chlordiazepoxide, zopiclone, pentobarbital and meprobamate produced chlordiazepoxide-appropriate responding. CGS 9896 also produced chlordiazepoxide-appropriate responding at a wide range of doses although the stimulus properties of this compound appeared to be weaker than those of the other active drugs. Chlordiazepoxide and zopiclone produced dose-related increases in food intake in food-deprived rats. CGS 9896 had similar effects at low doses but its effects were less consistent at higher doses. Thus, zopiclone has a behavioral profile very similar to that of chlordiazepoxide. Although many of the effects of CGS 9896 were similar to those of chlordiazepoxide, a number of differences were also observed.

Animals↗
PubMed1992

Modification of chlordiazepoxide's behavioural and neurochemical effects by handling and plus-maze experience.

The purpose of the present experiment was to determine how a rat's prior history (of repeated gentle handling and/or of the elevated plus-maze apparatus) modified the behavioural and neurochemical response to chlordiazepoxide. In handled animals one previous exposure to the plus-maze rendered the rats insensitive to the anxiolytic effects of chlordiazepoxide in this test. This phenomenon of 'one-trial tolerance' was not seen in unhandled rats and thus both prior handling and prior maze experience were necessary to abolish the behavioural response to chlordiazepoxide. The effects of chlordiazepoxide on K(+)-evoked [14C]GABA (gamma-aminobutyric acid) release were also modified by the rat's past history. The drug-induced reduction of GABA release in the cortex was abolished by prior plus-maze experience; whereas handling modified chlordiazepoxide's effects on GABA release in the hippocampus (the drug decreased release in unhandled rats and increased release in those given repeated gentle handling). Thus an anxiolytic response to chlordiazepoxide in the plus-maze was accompanied by reduced GABA release in both cortex and hippocampus. The 5-HT system (5-hydroxytryptamine) also proved sensitive to the rats' past history. The effects of chlordiazepoxide on K(+)-evoked [3H]5-HT release from the hippocampus depended on both prior handling and plus-maze experience and could be predicted from the undrugged level of evoked release; when this was low, chlordiazepoxide increased it, when it was high, chlordiazepoxide reduced it. These results raise the possibility that the beneficial effects of a benzodiazepine may depend on the baseline condition of the animals.

Animals↗
PubMed1993

Development of tolerance to amnesic effects of chlordiazepoxide in relation to GABAergic and cholinergic neuronal systems.

Chronic administration of benzodiazepines has been reported to produce tolerance in animals and humans. We investigated whether benzodiazepines produce tolerance to the amnesic effects and effects on benzodiazepine receptors, GABAergic and/or cholinergic neuronal systems of repeated administration of chlordiazepoxide, using a passive avoidance task and autoradiographic techniques. Tolerance developed to the amnesic effect of chlordiazepoxide when the drug was administered at a dose of 30 mg/kg (i.p.) once a day for 14 days. Bicuculline (1.0 and 1.5 mg/kg), a GABAA receptor antagonist, did not induce amnesia in normal mice, but did so in chlordiazepoxide-tolerant mice. Muscimol (0.25 mg/kg), a GABAA receptor agonist, in combination with a low dose of chlordiazepoxide, induced amnesia in normal mice, but not in chlordiazepoxide-tolerant mice. Scopolamine, an acetylcholine receptor antagonist, induced amnesia in normal mice, but not in chlordiazepoxide-tolerant mice. In the autoradiographical study, although repeated treatment with chlordiazepoxide had no effect on [3H]flunitrazepam and [3H]Ro 15-4513 binding to benzodiazepine receptors, it decreased [3H]muscimol binding to GABAA receptors, with a decrease in affinity in the cortex and hippocampus. Furthermore, repeated administration of chlordiazepoxide increased [3H]quinuclidinyl benzilate binding to muscarinic acetylcholine receptors in the hippocampus. These results suggest that tolerance develops to the amnesic effects of chlordiazepoxide, and that tolerance may be due to down-regulation of GABAA receptors and/or up-regulation of acetylcholine receptors.

Amnesia↗
PubMed1978

Chronic chlordiazepoxide and pentobarbital interactions on punished and unpunished behavior.

Dose-effect curves were determined in rats for the effects of drugs on punished and unpunished responding maintained by fixed-interval schedules of food presentation before, during and after the drinking of large daily doses of chlordiazepoxide and pentobarbital. An average intake of 50 mg/kg/day of chlordiazepoxide produced tolerance to the rate-decreasing effects of chlordiazepoxide on unpunished responding and cross-tolerance to the rate-decreasing effects of pentobarbital. During chlordiazepoxide drinking, rate-increasing effects of both chlordiazepoxide and pentobarbital on punished responding became apparent. There was no evidence for cross-tolerance between chlordiazepoxide and chlorpromazine. An average intake of 100 mg/kg/day of pentobarbital produced similar evidence of tolerance to the rate-decreasing effects of pentobarbital on unpunished responding and cross-tolerance to the rate-decreasing effects of chlordiazepoxide. Removal of chlordiazepoxide from the drinking water temporarily increased unpunished responding; however, 6 weeks after withdrawal of chlordiazepoxide or pentobarbital from the drinking water, the dose-effect curves for injections of these drugs appeared to be returning to their original positions.

Animals↗
PubMed1989

MR/Har and MNRA/Har Maudsley rat strains: differential response to chlordiazepoxide in a conflict task.

The Maudsley Reactive (MR/Har) and Non-Reactive (MNRA/Har) rat strains, selectively bred for differences in open field defecation, have also been shown to differ in their baseline behavior in the Conditioned Suppression of Drinking (CSD) procedure, a second "model" behavior for the study of anxiety and/or emotionality in rats. The present studies were designed to compare the responsiveness of these two strains to the typical antianxiety agent chlordiazepoxide in the CSD paradigm. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube that was occasionally electrified (0.5 mA), electrification being signaled by a tone. Consistent with previous reports, after several weeks of CSD testing, MNRA/Har rats accepted significantly more shocks than did MR/Har rats during control (nondrug) sessions. In both strains, the number of shocks accepted was inversely related to the intensity of the shock used (0.25-1.0 mA), with MNRA/Har rats accepting significantly more shocks than MR/Har rats at all intensities examined. The effects of various doses (1.25-28.4 mg/kg, IP) of chlordiazepoxide were determined in subjects of the MNRA/Har strain at the original training intensity (0.5 mA), while a lower intensity (0.25 mA) was utilized in MR/Har rats. Although punished responding in control (i.e., nondrug) CSD sessions did not differ under these conditions, MNRA/Har rats were found to be more responsive to the anticonflict effects of chlordiazepoxide than rats of the MR/Har strain. This strain difference in anticonflict efficacy of chlordiazepoxide was quite dramatic, with MNRA/Har rats accepting twice as many shocks as MR/Har rats following maximally effective doses of chlordiazepoxide. Low doses of chlordiazepoxide increased water intake slightly, while higher doses decreased water intake. Surprisingly, the chlordiazepoxide-induced depression of water intake was greater in rats of the MR/Har strain. Thus, these Maudsley Reactive and Non-Reactive rat strains, bred originally for their differences in open field behavior, also differ markedly in their responsiveness to chlordiazepoxide in the CSD paradigm. These findings further support the hypothesis that the MR/Har and MNRAHar rat strains may represent a genetically-based "animal model" for the study of emotionality and/or anxiety.

Animals↗
PubMed1993

Effects of intracranial infusions of chlordiazepoxide on spatial learning in the Morris water maze. I. Neuroanatomical specificity.

The present investigation sought to determine the neuroanatomical locus through which the amnesic and anxiolytic effects of the benzodiazepine agonist chlordiazepoxide are mediated. Rats were infused with either chlordiazepoxide (60 nmol/microliters) or artificial CSF (1 microliter) into either the frontal cortex, nucleus basalis magnocellularis/substantia innominata, amygdala, medial septum, hippocampus, or cerebellum and run in the open field to assess anxiety as thigmotaxia and in the Morris water maze to assess spatial learning. Other rats were given chlordiazepoxide (5 mg/kg) or saline (1 ml/kg) systemically and run in the open field and water maze. When chlordiazepoxide was administered systemically, rats showed significantly less thigmotaxia, but not overall activity, than controls in the open field, and were deficit in spatial learning, but not cue learning or swim speed, in the water maze. Intracranial infusions revealed a neuroanatomical specificity for the amnesic and anxiolytic actions of chlordiazepoxide. Infusions of chlordiazepoxide into the amygdala, but none of the other structures, reduced thigmotaxia without affecting overall activity levels whereas infusions into the medial septum, but none of the other structures, prevented spatial learning, but not cue learning, and reduced swim speed in the water maze. Together, these finding suggest that the medial septum and the amygdala mediate the amnesic and anxiolytic actions of chlordiazepoxide, respectively. Moreover, these results provide direct evidence that the amnesic and anxiolytic actions of chlordiazepoxide are independent.

Amnesia↗
PubMed1993

Tolerance to the behavioral effects of chlordiazepoxide: pharmacological and biochemical selectivity.

There is a dynamic interaction between a drug's pharmacological effects and the behavioral context in which it is administered. The present study evaluated the influence of behavioral processes on the development of tolerance and cross-tolerance to the rate-decreasing effects of chlordiazepoxide in rats. Sprague-Dawley rats responded under a fixed-ratio 30 schedule of food delivery. Different groups of rats received 18 mg/kg/day of chlordiazepoxide either before (PRE, n = 8) or after (POST, n = 10) daily experimental sessions for 8 weeks. Cumulative dose-response curves for chlordiazepoxide were obtained before and during chronic chlordiazepoxide administration and during chronic saline administration. Cumulative dose-response curves for midazolam, FG 7142 (N-methyl-beta-carboline-3-carboxamide) flumazenil, pentobarbital, caffeine, morphine and d-amphetamine were determined before, during and 4.5 to 5 months after chronic chlordiazepoxide administration. Group PRE developed tolerance to chlordiazepoxide, whereas group POST did not develop tolerance. Although cross-tolerance developed to midazolam in both groups, it was greater in group PRE. Both groups showed comparable sensitization to FG7142 and neither group showed a significant change in sensitivity to any of the other drugs. Biochemical studies of gamma-aminobutyric acid (GABA)-related functioning in groups of rats that received chronic chlordiazepoxide administration either before (BIO-PRE, n = 6) or after (BIO-POST, n = 6) daily sessions found that GABA-stimulated 36Cl-uptake increased in both cortical and cerebellar preparations. However, GABA sensitivity in cerebellar tissue was significantly lower in group BIO-PRE compared with group BIO-POST. Thus, behavioral tolerance to chlordiazepoxide was associated with both pharmacological and biochemical effects, which suggests a relationship between behavioral tolerance to benzodiazepines and changes in the functional state of the GABA-benzodiazepine receptor complex.

Amphetamine↗
PubMed1993

Chlordiazepoxide block of two types of calcium channels in neuroblastoma cells.

Chlordiazepoxide is a benzodiazepine that is widely used as a minor tranquilizer. It is also effective in the treatment of acute alcohol withdrawal. In this setting, chlordiazepoxide acts as a sedative and prevents the development of epileptiform activity. Although benzodiazepines are known to augment gamma-aminobutyric acid-activated chloride channels, an action which at least partially accounts for their anticonvulsant properties, there is some evidence to suggest that voltage-activated calcium channels may also be the target of these agents. We therefore studied the effect of chlordiazepoxide in blocking two distinct types of voltage-activated calcium channels in N1E-115 neuroblastoma cells. Chlordiazepoxide reversibly blocked calcium channels in both closed and open configurations. It was slightly more potent in blocking the transient (T-type or type I) than the long-lasting (L-type or type II) type of calcium channels with apparent Ki values of 311 and 398 microM, respectively. In the presence of chlordiazepoxide, the currents of both types of calcium channel currents decayed more quickly than control, an observation that suggests open channel block. Chlordiazepoxide-induced block of T-type calcium channels was use dependent, increasing with an increase in stimulus frequency. This was due primarily to the acceleration of current decay and slowing of recovery from inactivation by chlordiazepoxide. These calcium channel blocking actions could contribute some to the sedative and anticonvulsant properties of chlordiazepoxide in patients suffering from acute alcohol withdrawal and in electric shock-induced seizures in animal models.

Animals↗
PubMed1981

The effects of chlordiazepoxide on synaptic transmission and amino acid neurotransmitter release in slices of rat olfactory cortex.

The rat olfactory cortex slice has been used to investigate the effects of chlordiazepoxide on evoked field potentials and the release of endogenous amino acid neurotransmitters (aspartate, glutamate, GABA and possibly taurine) which accompany electrical stimulation of the lateral olfactory tract. When single, low frequency stimuli were employed, chlordiazepoxide (2 microM-1 mM) depressed the amplitude of the field potential correlate of the depolarizing actions of the lateral olfactory tract excitatory transmitter (aspartate?) although aspartate release was unaffected. The field potential correlate of GABA-mediated presynaptic inhibition (late N-wave) was also depressed in amplitude but low drug concentrations (between approximately 2 and 50 microM) increased its peak duration . Effects of chlordiazepoxide on evoked inhibition were analyzed by giving paired stimuli such that the second stimulus occurred during the field potentials evoked by the first stimulus. Chlordiazepoxide (1-20 microM) increased the depression in amplitudes of the presynaptic massed action potential and late N-wave evoked by the second of a pair of stimuli compared with those evoked by the first stimulus suggesting that presynaptic inhibition was potentiated. These effects of chlordiazepoxide were accompanied by a significant reduction in aspartate release from the lateral olfactory tract terminals. Moreover, the drug effects on presynaptic inhibition and aspartate release were antagonized by picrotoxin (5 microM). On the other hand, chlordiazepoxide (1-50 microM) had no significant effect on postsynaptic inhibition. The results are discussed in terms of both the sites (presynaptic or postsynaptic) and mechanisms of action of chlordiazepoxide.

4-Aminobutyrate Transaminase↗
PubMed1993

A phase-response curve to the benzodiazepine chlordiazepoxide and the effect of geniculo-hypothalamic tract ablation.

The geniculo-hypothalamic tract (GHT) provides input to the mammalian circadian pacemaker in the suprachiasmatic nucleus. Several recent reports indicate that GHT ablation blocks phase shifts to the benzodiazepines triazolam and chlordiazepoxide at circadian times (CTs) 6 and 21. In this study we tested if GHT ablation blocks phase shifts to chlordiazepoxide at a wide range of circadian phases. Syrian hamsters were housed under constant dim light, and running-wheel activity rhythms were monitored. Intraperitoneal injections of either chlordiazepoxide (100 mg/kg) or saline were administered at various circadian times, and a phase-response curve was constructed. In intact animals, chlordiazepoxide produced phase-advance shifts at CTs 0, 4, 6, and 8, and phase-delay shifts between CTs 12-14. Although bursts of increased activity were sometimes observed on the day of injection, activity does not appear to mediate chlordiazepoxide-induced phase shifts. Hamsters with > 45% GHT ablation showed no phase shifts > 20 min to chlordiazepoxide. Our results indicate that the geniculo-hypothalamic tract is necessary for the phase-shifting effects of the benzodiazepine chlordiazepoxide throughout the circadian cycle.

Animals↗