Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study.
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OBJECTIVE: To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures. DESIGN: Prospective randomised study. SETTING: Paediatric emergency department in a general hospital. SUBJECTS: 47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period. INTERVENTIONS: Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg). MAIN OUTCOME MEASURES: Time from arrival at hospital to starting treatment and cessation of seizures. RESULTS: Intranasal midazolam and intravenous diazepam were equally effective. Overall, 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam. The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the diazepam group (8.0 (0.5), 7. 9 to 8.3). No significant side effects were observed in either group. CONCLUSION: Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam, although midazolam was as safe and effective as diazepam. The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam. The intranasal route can possibly be used not only in medical centres but in general practice and, with appropriate instructions, by families of children with recurrent febrile seizures at home. (+info)
Chronic exposure to ethanol alters GABA(A) receptor-mediated responses of layer II pyramidal cells in adult rat piriform cortex.
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This study examined the effect of chronic exposure to ethanol on gamma-aminobutyric acid type-A (GABA(A)) receptor-mediated responses of layer II pyramidal neurons of the piriform cortex. Slices containing the piriform cortex were derived from pair-fed adult rats maintained on ethanol-supplemented or control liquid diet for 30 days. Responses of identified layer II pyramidal neurons to exogenously applied GABA were monitored by whole-cell patch-clamp recording. Chronic exposure to ethanol resulted in a rightward shift in the EC(50) of GABA and a decrease in the amplitude of maximal GABA response. GABA-induced responses were modulated by acutely applied ethanol (10-100 mM) in both chronic ethanol-treated and control groups. No significant difference was found in the average change in GABA response, suggesting that tolerance to acute ethanol exposure did not develop. When the modulatory responses of individual cells were classified and grouped as either being attenuating, potentiating, or having no effect, the incidence of potentiation in the ethanol-treated group was significantly higher. Consistent with the absence of tolerance to acute ethanol, cross-tolerance to diazepam was not observed following 30 days of treatment with ethanol. These results are discussed in light of regionally specific effects of chronic ethanol treatment on GABA(A) receptor-mediated responses of layer II piriform cortical neurons. (+info)
Behavioral effects of plant-derived essential oils in the geller type conflict test in mice.
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The present study was conducted to further explore plant-derived essential oils that possess an anticonflict effect using the Geller type conflict test in ICR mice. The benzodiazepine anxiolytic diazepam increased the response (lever pressing) rate during the alarm period (i.e., an anticonflict effect), but the 5-HT1A partial agonist buspirone did not. Oils of juniper, cypress, geranium and jasmine did not produce any effect in this test. Frankincense oil decreased the response rate during the safe period at 1600 mg/kg, but did not exhibit any effect on the response rate during the alarm period. In contrast, lavender oil increased the response rate during the alarm period in a dose-dependent manner in the same manner as diazepam. These results indicate that not only rose oil but also lavender oil possess an anticonflict effect in mice. (+info)
Psychomotor skills related to driving after intramuscular administration of diazepam and meperidine.
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Psychomotor skills related to driving and the ability to discriminate the fusion of flickering light were measured in a double-blind cross-over fashion in 11 healthy volunteers before, and 1, 3, 5, and 7 hours after, intramuscular injection of saline solution, 10 mg diazepam, or 75 mg meperidine. The late effects of meperidine were tested in five other subjects 12 and 24 hours after the injection. The effects of diazepam were the most harmful to coordinative and reactive skills, which were significantly impaired for as long as 5 hours. Meperidine impaired reactive skills for as long as 3 hours and flicker-fusion discrimination and coordinative skills for as long as 12 hours. It is concluded that patients should not drive or operate machinery for at least 7 hours after receiving 10 mg diazepam intramuscularly and for 24 hours after receiving 75 mg meperidine intramuscularly. (+info)
Antagonism of the discriminative stimulus effects of positive gamma-aminobutyric acid(A) modulators in rhesus monkeys discriminating midazolam.
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The extent to which individual subtypes of benzodiazepine receptors are functionally independent has not been elucidated in vivo. This study used apparent pA(2) analysis to test the hypothesis that a single receptor subtype mediates the discriminative stimulus effects of midazolam, triazolam, and diazepam, three positive gamma-aminobutyric acid(A) (GABA(A)) modulators. Four rhesus monkeys discriminated 0.56 mg/kg midazolam from vehicle under a fixed-ratio 5 schedule of stimulus-shock termination. Midazolam, triazolam, and diazepam increased responding on the midazolam-appropriate lever. The neutral GABA(A) modulator flumazenil shifted dose-effect curves for triazolam and diazepam to the right, and the negative GABA(A) modulators Ro 15-4513 and ethyl beta-carboline-3-carboxylate (beta-CCE) shifted dose-effect curves for midazolam and triazolam to the right. Slopes of Schild plots for flumazenil and Ro 15-4513 conformed to unity. The apparent pA(2) values were 7.41 and 7.69 for flumazenil in combination with triazolam and diazepam, respectively, and 7.53 and 6.88 for Ro 15-4513 in combination with midazolam and triazolam, respectively. The slope of the Schild plot for beta-CCE in combination with midazolam deviated from unity. Slopes of Schild plots obtained with flumazenil and Ro 15-4513 support the notion that a single benzodiazepine receptor subtype mediates the effects of midazolam, triazolam, or diazepam. The similarity in apparent pA(2) values for flumazenil in combination with triazolam and diazepam or for Ro 15-4513 in combination with midazolam and triazolam suggests that the same subtype mediates the effects of these positive modulators. In contrast, beta-CCE and midazolam do not appear to interact in a simple, competitive manner. (+info)
Enhanced anticonvulsant activity of ganaxolone after neurosteroid withdrawal in a rat model of catamenial epilepsy.
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Perimenstrual catamenial epilepsy, the exacerbation of seizures in association with menstruation, may in part be due to withdrawal of the progesterone metabolite allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), an endogenous anticonvulsant neurosteroid that is a positive allosteric modulator of gamma-aminobutyric acid(A) receptors. Neurosteroid replacement is a potential approach to therapy, but natural neurosteroids have poor bioavailability and may be converted to metabolites with undesired progestational activity. The synthetic neuroactive steroid ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnane-20-one) is an orally active analog of allopregnanolone that is not converted to the hormonally active 3-keto form. To assess the potential of ganaxolone in the treatment of catamenial seizure exacerbations, a state of persistently high serum progesterone (pseudopregnancy) was induced in 26-day-old female rats with gonadotropins, and neurosteroids were withdrawn on postnatal day 39 with finasteride, a 5alpha-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone. Finasteride treatment during pseudopregnancy results in a reduction in the threshold for pentylenetetrazol seizures. During this state of enhanced seizure susceptibility, there was a 3-fold increase in the anticonvulsant potency of ganaxolone (control ED(50) = 3.5 mg/kg; withdrawn = 1.2 mg/kg) without a change in the potency for induction of motor toxicity in the rotarod test. The plasma concentrations of ganaxolone did not differ significantly in control and withdrawn animals; the estimated plasma concentrations of ganaxolone producing 50% seizure protection were approximately 500 and approximately 225 ng/ml in control and withdrawn rats, respectively. Unlike ganaxolone, neurosteroid withdrawal was associated with a decrease in the anticonvulsant potency of diazepam (control ED(50) = 1.9 mg/kg; withdrawn = 4.1 mg/kg) and valproate (control ED(50) = 279 mg/kg; withdrawn = 460 mg/kg). The enhanced anticonvulsant potency of ganaxolone after neurosteroid withdrawal supports the use of ganaxolone as a specific treatment for perimenstrual catamenial epilepsy. (+info)
Pentobarbital modulates gamma-aminobutyric acid-activated single-channel conductance in rat cultured hippocampal neurons.
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We examined the effect of a range of pentobarbital concentrations on 0.5 microM gamma-aminobutyric acid (GABA)-activated channels (10 +/- 1 pS) in inside-out or outside-out patches from rat cultured hippocampal neurons. The conductance increased from 12 +/- 4 to 62 +/- 9 pS as the pentobarbital concentration was raised from 10 to 500 microM and the data could be fitted by a Hill-type equation. At 100 microM pentobarbital plus 0.5 microM GABA, the conductance seemed to reach a plateau. The pentobarbital EC(50)(0.5 microM GABA) value was 22 +/- 4 microM and n was 1.9 +/- 0.5. In 1 mM pentobarbital plus 0.5 microM GABA, the single-channel conductance decreased to 34 +/- 8 pS. This apparent inhibition of channel conductance was relieved by 1 microM diazepam. The channel conductance was 64 +/- 6 pS in the presence of all three drugs. The channels were open more in the presence of both GABA and pentobarbital than in the presence of either drug alone. Pentobarbital alone (100 microM) activated channels with conductance (30 +/- 2 pS) and kinetic properties distinct from those activated by either GABA alone or GABA plus pentobarbital. Whether pentobarbital induces new conformations or promotes conformations observed in the presence of GABA alone cannot be determined from our study, but the results clearly show that it is the combination of drugs present that determines the single-channel conductance and the kinetic properties of the receptors. (+info)
A 3 year case study of alcohol related psychotic disorders at Hospital Seremban.
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This paper reports the characteristics and psychopathology of alcohol dependents with alcohol induced psychotic disorder admitted to the Seremban Hospital. The method is that of a case study of all alcohol dependents with alcohol induced psychotic disorder admitted to the Psychiatric Ward, Hospital Seremban over 3 years (1993-1995). There were 34 subjects, 30 Indians, 3 Chinese and 1 Malay with a mean age of 43 years. 32 were men and predominantly of Social Class IV and V (91%). They had a mean duration of drinking of 14.2 years and had a mean weekly consumption of 69.5 units of alcohol. There was a family history of alcohol dependence in (44%). The majority (68%) consumed samsu with beer the second choice. Auditory hallucinations (26) and delusions (16) were common while visual hallucinations (3) and depression (2) were less frequent. Speech disorder occurred in 4 subjects. 2 developed delirium tremens and 1 died. Liver function test was normal in 55%. All except the death from delirium tremens responded to treatment with a combination of anxiolytics, thiamine and antipsychotics and were rapidly discharged. The mean stay was 7 days. However, (68%) did not return for follow up and only 4 were abstinent from alcohol at the time of follow up. (+info)