Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DIAZEPAM”

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 469 records · Page 26Linked to original sources
PubMed2002

The anxiolytic action of mGlu2/3 receptor agonist, LY354740, in the fear-potentiated startle model in rats is mechanistically distinct from diazepam.

The fear-potentiated startle paradigm has been characterized for drugs that act via ionotropic (NMDA and AMPA/kainate receptor) glutamate receptor mechanisms. Previous studies have shown that the potent systemically active mGlu2/3 receptor agonist, LY354740, effectively reduced the expression of fear-potentiated startle responses in rats. The present study examined the effects of LY354740 in a pre- versus post-fear conditioning paradigm and compared the effects to diazepam. Diazepam (0.3, 0.6, and 1.0 mg/kg ip) attenuated both pre- and post-fear conditioning startle responses in a dose-related manner. In contrast, LY354740 (0.03, 0.3, and 3.0 mg/kg ip) did not disrupt preconditioning startle responses at doses that attenuated post-fear conditioning responses. The benzodiazepine antagonist, flumazenil, at a dose (2 mg/kg sc) that did not alter fear-potentiated startle per se, selectively reversed suppression of fear responses to diazepam (0.6 mg/kg ip) while not affecting fear suppression induced by LY354740 (0.3 mg/kg ip). At a dose of 1 mg/kg ip, the mGlu2/3 receptor antagonist, LY341495, did not disrupt fear-enhanced startle per se, but completely reversed the postconditioning anxiolytic effects of LY354740 in this model. This dose of LY341495 had no effect on fear suppression by diazepam. These results demonstrate that fear suppression by diazepam and LY354740 involves different neuronal mechanisms. While diazepam acts via the facilitation of GABAergic transmission, LY354740 induces its actions via the glutamatergic system, specifically mGlu2/3 receptor activation. Furthermore, in contrast to disruption of fear conditioning as well as fear suppression by diazepam, LY354740 had selective effects on fear expression, suggesting anxiolytic actions without the associated memory impairment.

Acoustic Stimulation↗
PubMed1992

Subcortical deterioration after cortical damage: effects of diazepam and relation to recovery of function.

Agents which enhance the activity of gamma-aminobutyric acid (GABA) can severely disrupt behavioral recovery in rats following damage to the neocortex if delivered during a sensitive postoperative period. The mechanisms of this disruption have not been found. It has been suggested previously that the ipsilateral striatum and related structures may be transiently disabled after cortical lesions and that diazepam may interfere with restoration of function in these areas. In the present experiment, the subcortical anatomical effects of chronic (3 weeks) administration of diazepam, an indirect GABAergic agonist, were assessed following unilateral lesions of the anteromedial cortex (AMC) or the sensorimotor cortex (SMC) in rats. Atrophic and degenerative changes were examined in the striatum, substantia nigra and thalamus. Following either AMC or SMC lesions, there was a reduction in the size of the ipsilateral striatum and thalamus and a loss of neurons in the ipsilateral substantia nigra pars reticulata (SNr). After AMC lesions, striatal atrophy and neuron loss in the SNr were increased by the diazepam regimen relative to vehicle-treated controls. In addition, diazepam interfered with the behavioral recovery from somatic-sensorimotor asymmetries in AMC-lesioned rats. After SMC lesions, the sites of striatal and thalamic atrophy were different from that observed after AMC lesions, and the extent of atrophy and neuron loss was not exaggerated by diazepam treatment. Consistent with these data, diazepam did not significantly affect recovery from SMC lesions. These findings suggest that the long-term disruptive effects of diazepam on recovery of function after AMC lesions may be related to an augmentation of lesion-induced degeneration.

Animals↗
PubMed2003

Diazepam and progesterone produce sexually dimorphic actions on the rat EEG: role of the neonatal sexual differentiation process.

This study was designed to analyse if the effect of diazepam or progesterone on the wakeful rat EEG vary according to sex and neonatal sexual differentiation. Diazepam or progesterone was administered to males, females, neonatally castrated males and neonatally virilised females. Comparisons of drug actions were made versus baseline values. Both compounds produced clear sexual dimorphic responses, males being more sensitive than females. In normal males and neonatally virilised females diazepam produced a clear increase in the absolute power of fast frequencies. In normal females and neonatally castrated males this anxiolytic only produced a moderate increase in the absolute power of the beta 2 band. Regarding interparietal correlation, diazepam produced an increase in males in the alpha, beta 1 and beta 2 bands, while in females this drug caused a reduction in the same bands. Neonatally castrated males or virilised females showed an intermediate pattern. These data suggest that sexual dimorphism in diazepam action depends upon neonatal sexual differentiation. Progesterone, in contrast with diazepam, produced effects on the EEG that were also sexually dimorphic but independent of the sexual differentiation process. This steroid in males induced an increase in the absolute power of the fast bands of the EEG (alpha, beta 1 and beta 2) accompanied by an increased interparietal correlation of the alpha band. In females, progesterone only reduced the interparietal correlation in the fast theta and alpha bands. Data show similarities between diazepam and progesterone effects on the EEG that are discussed in the light of the anxiolytic-like and hypnotic properties of these compounds. A similar mechanism of action for both substances, involving the GABA(A) receptor, is sustained.

Animals↗
PubMed1998

Effect of diazepam and sex hormones on EEG of gonadectomized male and female rats.

Waking EEG was recorded from left and right parietals in 60 adult Wistar rats gonadectomized after puberty during 5 days, 1 as baseline, 1 with vehicle and 1 with 10 mg/kg i.m. of diazepam with hormonal treatment (either testosterone propionate, 5-alpha-dihydrotestosterone or vehicle in males and progesterone, estradiol benzoate or vehicle in females). Quantitative EEG analysis showed that: diazepam in gonadectomized males increased absolute power of alpha, beta 1 and beta 2, increased interparietal correlation of delta and decreased interparietal correlation of slow theta, fast theta and beta 1, whereas in gonadectomized females, diazepam additionally decreased slow and fast theta absolute power. EEG effects were not modified by testosterone propionate or 5-alpha-dihydrotestosterone treatment in males. Diazepam plus estradiol rendered the female EEG response similar to the gonadectomized or testosterone-treated males response; diazepam plus progesterone induced the same response in females as in gonadectomized females and additionally induced interparietal asymmetry and decreased interparietal correlation of all EEG bands. Present results and information on the effects of diazepam on interparietal coupling of EEG and demonstrate that the EEG response to diazepam in adult rats is sexually dimorphic and depends on sex as well as on activational effects of gonadal steroids.

Animals↗
PubMed1998

Effects of oral diazepam on intravenous access in same day surgery patients.

STUDY OBJECTIVE: To determine the effects of 5 mg oral diazepam on vein quality, patient anxiety, and intravenous (i.v.) access. DESIGN: Prospective, randomized, double-blind, placebo controlled study. SETTING: Preoperative holding area of a large university hospital. PATIENTS: 202 adult ASA physical status I, II, and III patients scheduled for elective outpatient surgery. INTERVENTIONS: Patients were randomized to receive either 5 mg oral diazepam or placebo, 30 minutes prior to i.v. access. MEASUREMENTS AND MAIN RESULTS: Vein quality and patient anxiety were assessed prior to, and 30 minutes following, premedication (just prior to venipuncture) using a 5 point ordinal scale and 10 cm visual analog scale, respectively. The number of attempts at venous access and the gauge of the catheter used were also recorded. Baseline patient anxiety was similar between the two groups and both showed a significant improvement in patient anxiety at 30 minutes following drug administration. The diazepam group, however, had a significantly greater reduction in anxiety scores (p < 0.05). There were no differences in baseline vein quality between the two groups; however, the quality of the vein was subjectively improved following diazepam administration. The mean number of attempts at i.v. access between the diazepam group (1.26 +/- 0.56) and the placebo group (1.32 +/- 0.65) was not significantly different. However, the ability to place larger gauge catheters was significantly enhanced in the diazepam group. CONCLUSIONS: The administration of 5 mg oral diazepam prior to the establishment of i.v. access improved vein quality and decreased patient anxiety. This technique may be a useful method for i.v. catheter placement, particularly when large gauge catheters are required, or when difficult i.v. access is anticipated.

Adjuvants, Anesthesia↗
PubMed2006

A prospective comparative study to examine the effects of oral diazepam on blood pressure and anxiety levels in patients with acute epistaxis.

OBJECTIVE: To examine the effects of oral diazepam on blood pressure and anxiety in patients with acute epistaxis. STUDY DESIGN AND SETTING: A prospective comparative study in an otorhinolaryngology tertiary referral centre. PARTICIPANTS: Patients with acute epistaxis requiring hospital admission. INTERVENTION: Oral diazepam. MAIN OUTCOME MEASURES: Anxiety and blood pressure levels. RESULTS: 32 patients received diazepam and 45 did not (control). On average, patients were hypertensive on admission (mean [standard deviation (SD)] systolic blood pressure diazepam group=157 mmHg [26], control=152 mmHg [23]; diastolic blood pressure diazepam group=87 mmHg [16], control=87 mmHg [18]). Both groups showed significant blood pressure reduction on discharge (p<0.0001) but the difference in mean blood pressure reduction between the two groups was insignificant (systolic blood pressure p=0.16, 95% confidence interval [CI]=-5 to +19 mmHg; diastolic blood pressure p=0.43, 95% CI=-8 to +10 mmHg). Anxiety was significantly lower on discharge (p<0.0001) but the difference in mean fall in anxiety scores between the two groups was insignificant (p=0.08, 95% CI=0 to +2). There was no significant correlation between total diazepam and changes in blood pressure (systolic blood pressure p=0.32; diastolic blood pressure p=0.65) or anxiety (p=0.73), nor between blood pressure and anxiety on admission (systolic blood pressure p=0.45; diastolic blood pressure p=0.72). CONCLUSIONS: Elevated blood pressure and anxiety in acute epistaxis patients reduced on epistaxis resolution irrespective of oral diazepam use. The elevated blood pressure does not appear to be directly related to anxiety.

Adolescent↗
PubMed1995

Enhanced transdermal delivery of diazepam by submicron emulsion (SME) creams.

Diazepam, a lipophilic drug with CNS activity, serves here as a model to investigate the efficacy of SubMicron Emulsion (SME) as a novel transdermal vehicle. Diazepam was formulated in various topical regular creams and SubMicron Emulsion creams of different compositions. The different formulations were applied topically and protection against Pentamethylenetetrazole induced convulsive effects in mice was monitored. The efficacy of Diazepam applied topically in emulsion creams strongly depends on the oil droplet size and to a lesser degree--on the formulation composition and the oil type. Processing medium-chain-triglyceride (MCT) emulsion with a high-pressure homogenizer causes a drastic reduction in the droplet size, thereby significantly increasing the transdermal activity of Diazepam. In this case both the high-pressure homogenization and the presence of lecithin, an efficient dispersant, contribute to the effective droplet size reduction of below 1 micron, usually between 100-300 nm. The SubMicron Emulsions as vehicles for transdermal delivery of Diazepam generate significant systemic activity of the drug as compared with regular creams or ointments. Transdermal delivery of Diazepam via SME formulations is very effective, and the activity may reach the range of parenteral delivery. A single application of Diazepam in SME cream to mice skin provides pronounced transdermal drug delivery and prolonged protective activity up to 6 hours.

Administration, Cutaneous↗
PubMed2003

Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme.

Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavours, with low response rates and survival rarely exceeding 6 months. There are no standard chemotherapeutic regimens and new therapeutic approaches have to be found. We report an open-label, uncontrolled, multicentre phase II trial of lonidamine (LND) and diazepam in 16 patients with GBM at first relapse and a Karnofsky performance status > or = 70. The treatment regimen consisted of LND 450 mg/day and diazepam 15 mg/day orally of every 28-day cycle until progression or unacceptable toxicity. Patients received a median of three cycles (range, 1-12). No complete or partial response was observed. Therefore, according to the design of the study, no additional patients were enrolled and the trial was closed. Nevertheless, seven stabilizations (50%) were observed. Median time to progression was 8 weeks (range, 5-19 weeks). Median overall survival from recurrence was 15 weeks (range, 14-61 weeks). No grade 3-4 toxicity, except somnolence, was observed and there were no therapy-related deaths. Dose reduction for diazepam due to somnolence (grade III) was performed in 9 patients. The combination of LND and diazepam is well tolerated. LND and diazepam, acting on two distinct mitochondrial sites involved in cellular energy metabolism, may exert a cytostatic effect on tumour growth as shown by the high percentage of stable patients. The LND-diazepam at the used dosing schedule did not show a complete or partial response. LND plus diazepam may be interesting in the adjuvant setting or associated to chemotherapy to act on different targets and increase the therapeutic index.

Adult↗
PubMed1992

Incidence of S-mephenytoin hydroxylation deficiency in a Korean population and the interphenotypic differences in diazepam pharmacokinetics.

We studied the genetically determined hydroxylation polymorphism of S-mephenytoin in a Korean population (N = 206) and the pharmacokinetics of diazepam and demethyldiazepam after an oral 8 mg dose of diazepam administered to the nine extensive metabolizers and eight poor metabolizers recruited from the population. The log10 percentage of 4-hydroxymephenytoin excreted in the urine 8 hours after administration showed a bimodal distribution with an antimode of 0.3. The frequency of occurrence of the poor metabolizers was 12.6% in the population. In the panel study of diazepam in relation to the mephenytoin phenotype, there was a significant correlation between the oral clearance of diazepam and log10 urinary excretion of 4-hydroxymephenytoin (rs = 0.777, p less than 0.01). The plasma half-life of diazepam in the poor metabolizers was longer than that in the extensive metabolizers (mean +/- SEM, 91.0 +/- 5.6 and 59.7 +/- 5.4 hours, p less than 0.005), and the poor metabolizers had the lower clearance of diazepam than the extensive metabolizers (9.4 +/- 0.5 and 17.0 +/- 1.4 ml/min, p less than 0.001). In addition, the plasma half-life of demethyldiazepam showed a statistically significant (p less than 0.001) difference between the extensive metabolizers (95.9 +/- 11.3 hours) and poor metabolizers (213.1 +/- 10.7 hours), and correlated with the log10 urinary excretion of 4-hydroxymephenytoin (rs = -0.615, p less than 0.01). The findings indicate that the Korean subjects have a greater incidence of poor metabolizer phenotype of mephenytoin hydroxylation compared with that reported from white subjects and that the metabolism of diazepam and demethyldiazepam is related to the genetically determined mephenytoin hydroxylation polymorphism in Korean subjects.

Adult↗
PubMed1994

Inhibition of diazepam metabolism by fluvoxamine: a pharmacokinetic study in normal volunteers.

The effect of fluvoxamine on the pharmacokinetics of diazepam and metabolically derived N-desmethyl-diazepam was investigated in eight healthy volunteers. Each subject received a single oral dose of diazepam (10 mg) in a control session and on the fourth day of a 16-day treatment with fluvoxamine maleate (100 to 150 mg daily). Compared with the control session, concurrent fluvoxamine intake was associated with increased mean peak plasma diazepam concentrations (from 108 to 143 ng/ml, geometric means, difference not significant), with a marked reduction in apparent oral diazepam clearance (from 0.40 to 0.14 ml/min/kg; p < 0.01) and with a prolongation in diazepam half-life (from 51 to 118 hours; p < 0.01). Although peak plasma N-desmethyldiazepam levels were similar in the two sessions, the time required for the metabolite to reach a peak was longer during fluvoxamine intake than in the control session (206 versus 62 hours; p < 0.01). N-Desmethyldiazepam area under the plasma concentration-time curve values were also significantly increased during fluvoxamine treatment. These data suggest that fluvoxamine inhibits the biotransformation of diazepam and its active N-demethylated metabolite. The magnitude of this interaction is likely to have considerable clinical significance.

Adult↗
PubMed2001

Diazepam increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity by a cyclic AMP-dependent mechanism.

1. Previous studies in this laboratory have shown that diazepam behaves as a phosphodiesterase 4 (PDE 4) inhibitor. It has been reported that PDE-4 inhibitors activate the hypothalamic-pituitary-adrenocortical (HPA) axis in the rat. In the present study we have examined whether activation of the cyclic AMP-dependent protein kinase (PKA) is involved in the effect of diazepam on basal HPA axis activity. 2. Acute systemic administration of diazepam (10 mg kg(-1) i.p.) was found to increase the basal HPA axis activity, increasing the plasma concentrations of corticotrophin (ACTH) and corticosterone 30 min post injection. Diazepam also elevated cyclic AMP content of the hypothalamus. 3. Pretreatment of the animals with dexamethasone (1 mg kg(-1) s.c.) for 3 days completely abolished the effect of diazepam on HPA axis activity. 4. The antagonists of central and peripheral benzodiazepine receptors, flumazenil (10 mg kg(-1) i.p.) and PK 11195 (5 mg kg(-1) i.p.) did not affect the diazepam induced increase of HPA axis activity nor did they have an effect per se. 5. The increase in ACTH and corticosterone levels was significantly reduced by the cyclic AMP-dependent protein kinase (PKA) inhibitor, H-89, given either subcutaneously (5 mg kg(-1) s.c.) or intracerebroventricularly (i.c.v.; 28 microg in 10 microl). 6. The results indicate that diazepam can stimulate basal HPA axis activity in the rat by a cyclic AMP-dependent PKA mediated pathway.

Adrenal Cortex↗
PubMed2000

Detection of diazepam in horse hair samples by mass spectrometric methods.

A method for the detection of diazepam in horse hair samples by low resolution gas chromatography-mass spectrometry (GC-MS) was developed. Two other techniques, gas chromatography-high-resolution mass spectrometry (GC-HRMS) and high-performance liquid chromatography-atmospheric pressure chemical-ionisation mass spectrometry (HPLC-APCI-MS-MS) were applied on some selected samples. Sample preparation was performed according to a technique previously described for human hair, involving incubation with Sorensen buffer and solvent extraction. Hair samples from different sites such as coat on the neck, coat on the back, mane and tail were collected from two thoroughbreds which had received several dosages of diazepam corresponding to a total dose of 750 mg and 200 mg of diazepam respectively. In the first experiment, by low resolution GC-MS using single ion monitoring, diazepam was detected in the mane for at least 85 d after the last administration. In the second one, using the same method, diazepam was detected in the coat on the neck up to 25 d following the last administration. Low resolution GC-MS data were confirmed by the two other techniques. Furthermore, GC-HRMS even made possible the detection of diazepam up to 38 d after the administration of 200 mg of diazepam.

Animals↗
PubMed1980

The effect of age on the pharmacokinetics of diazepam.

1. After intravenous administration to 19 subjects, aged 18-95 years, plasma diazepam concentrations were measured over 160 h. Plasma protein binding of diazepam was also measured in each subject. 2. The terminal plasma half-life of diazepam ranged from 15.0 to 125 h and was positively correlated with age (r = 0.797). Total plasma diazepam clearance was not correlated with age (r = -0.017). 3. The free fraction of diazepam ranged from 0.0137 to 0.0386 and was significantly correlated with age (r = +0.863). Free diazepam clearance, which ranged from 432 to 1870 ml/min, was also correlated with age (r = -0.717). 4. It is concluded that the increased sensitivity of the elderly to diazepam is, at least in part, due to pharmacokinetic factors.

Adolescent↗
PubMed2001

Electroencephalographic effects and serum concentrations after intranasal and intravenous administration of diazepam to healthy volunteers.

AIMS: To evaluate the electroencephalographic (EEG) effects, blood concentrations, vehicle irritation and dose-effect relationships for diazepam administered nasally. METHODS: The study had a cross-over design with eight healthy volunteers (one drop out). It consisted of four legs with four different administrations: intranasal (i.n.) placebo, 4 mg diazepam i.n., 7 mg diazepam i.n. and 5 mg intravenous (i.v.) diazepam. Polyethylene glycol 300 (PEG300) was used as a vehicle in the nasal formulations to solubilize a clinically relevant dose of diazepam. Changes in N100, P200 and P300 brain event-related potentials (ERP) elicited by auditory stimulation and electroencephalographic beta-activity were used to assess effects on neurological activity. RESULTS: The mean [95% confidence intervals] differences between before and after drug administration values of P300-N100 amplitude differences were -0.9 [-6.5, 4.7], -6.4 [-10.1, -2,7], -8.6 [-11.4, -5.8] and -9.6 [-12.1, -7.1] for placebo, 4 mg i.n., 7 mg i.n. and 5 mg i.v. diazepam, respectively, indicating statistically significant drug induced effects. The bioavailabilities of 4 and 7 mg i.n. formulations, were found to be similar, 45% [32, 58] and 42% [22, 62], respectively. CONCLUSION: The present study indicates that it is possible to deliver a clinically effective nasal dose of diazepam for the acute treatment of epilepsy, using PEG300 as a solubilizer.

Administration, Intranasal↗
PubMed2003

The effect of variable-dose diazepam on dreaming and emergence phenomena in 400 cases of ketamine-fentanyl anaesthesia.

This randomised double-blind field study compared 400 anaesthetics using diazepam (0, 0.025, 0.5, 0.1, 0.175 mg.kg-1) with ketamine (1 mg.kg-1) and fentanyl (1 microg.kg-1) in Melanesian patients. Dreams were very common and generally positive in nature. A minimum of 0.1 mg.kg-1 of diazepam was needed to significantly reduce dreaming when compared with water (67.5% vs. 94.6%; p < 0.0001), and to significantly lower median (95% CI) emergence delirium scores (4 (3-4) vs. 6 (5-7)). Gender and age did not affect the rate of dreaming. Increasing the dose of diazepam did not improve the dream experience. Patient satisfaction scores were similar between groups. Increases in blood pressure and heart rate were greater in dreamers than in non-dreamers. All groups had high rate-pressure products but this was highest when diazepam was not used. Higher diazepam doses significantly reduced the increase in blood pressure and heart rate at 3 and 6 min postketamine. When used with ketamine and fentanyl, 0.1 mg.kg-1 of diazepam has favourable psychic and cardiovascular effects. Lower diazepam doses generally had little effect whereas larger doses did not enhance the benefits further.

Adjuvants, Anesthesia↗
PubMed1999

Effect of activated charcoal alone or given after gastric lavage in reducing the absorption of diazepam, ibuprofen and citalopram.

AIMS: The efficacy of activated charcoal alone, and gastric lavage followed by charcoal in reducing the absorption of diazepam, ibuprofen and citalopram was studied in healthy volunteers. METHODS: In a randomized cross-over study with three phases, nine healthy volunteers were administered single oral doses of 5 mg diazepam, 400 mg ibuprofen and 20 mg citalopram, taken simultaneously after an overnight fast. Thirty minutes later, the subjects were assigned to one of the following treatments: 200 ml water (control), 25 g activated charcoal as a suspension in 200 ml water or gastric lavage followed by 25 g charcoal in suspension given through the lavage tube. Plasma concentrations of diazepam, ibuprofen and citalopram were determined up to 10 h. RESULTS: The AUC(0,10 h) of diazepam was reduced by 27% (P<0.05) by both charcoal alone and charcoal combined with lavage. The increase in plasma diazepam concentration from 0.5 h onwards was prevented by both interventions (P</=0.05), whereas the Cmax of diazepam was not significantly affected by either treatment. The AUC(0, 10 h) of ibuprofen was reduced by 49% (P<0.05) after the combination treatment and by 30% (P<0.05) after charcoal alone, but there was no significant difference between these two treatments. Both charcoal alone and the combination treatment were equally effective in preventing the increase in plasma ibuprofen from 0.5 h onwards (P<0.01). The Cmax of ibuprofen was reduced by 45% (P<0.05) and by 21% (P=NS), respectively. The AUC(0,10 h) of citalopram was reduced by 51% (P<0.05) after both charcoal alone and charcoal combined with lavage, and the Cmax by 52% (P<0.05) and 54% (P<0.05), respectively. The increase in plasma citalopram concentration from 0.5 h onwards was reduced by about 50% (P<0.01) by both interventions. CONCLUSIONS: Activated charcoal alone and charcoal combined with lavage showed similar efficacy in preventing the absorption of diazepam, ibuprofen and citalopram. These results suggest that gastric lavage needs not be routinely performed before administration of charcoal.

Adult↗
PubMed1998

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers.

Zolmitriptan (Zomig) is a 5HT1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg + diazepam 10 mg, zolmitriptan 5 mg + diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.

Adult↗
PubMed1999

Diazepam and buspirone alter neuropeptide Y-like immunoreactivity in rat brain.

Neuropeptide Y-like immunoreactivity (NPY-LI) was investigated in naIve Sprague-Dawley rats subjected to acute, subchronic (7 days) or chronic (21 days) intraperitoneal treatment with diazepam (1 or 3 mg/kg once daily) or buspirone (1.5 or 5 mg/kg twice daily). NPY-LI was determined by radioimmunoassay in the amygdala, nucleus accumbens, hypothalamus and frontal cortex 24 h after the last dose of the drugs. Amygdala NPY-LI decreased after acute diazepam (3 mg/kg) or buspirone (1.5 mg/kg) and increased after subchronic treatment with both doses of diazepam and after chronic buspirone (1.5 mg/kg) treatment. Both diazepam and buspirone given in subchronic and chronic doses decreased NPY-LI levels in the nucleus accumbens. Hypothalamic NPY-LI changed only after chronic treatment: it decreased after diazepam and increased after buspirone (5 mg/kg). NPY-LI content in the frontal cortex decreased after subchronic diazepam (3 mg/kg) treatment and slightly increased after buspirone. The study has shown that both diazepam and buspirone affect NPY-LI levels in rats. These results suggest that the NPY system in the amygdala and nucleus accumbens is implicated in the anxiolytic effects of the drugs studied.

Amygdala↗