Serum Concentrations of Diazepam in Subjects With Epilepsy

Booker, Harold E.; Celesta, Gastone G.

doi:10.1001/archneur.1973.00490270073012

Cited by 74 publications

(21 citation statements)

References 5 publications

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“…Several investigators have demonstrated a reduction of inter-ictal spikes following single doses of intravenous diazepam (Neidermeyer, 1970;Booker & Celesia, 1973) but Ahmad et al (1977) were the first to suggest that spike counting could be used for the short term assessment of new compounds given intravenously. By modifying the method of Ahmad et al.…”

Section: Introductionmentioning

confidence: 99%

Acute effects of intravenous phenytoin on the frequency of inter‐ictal spikes in man.

Milligan¹,

Oxley²,

Richens³

1983

Brit J Clinical Pharma

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1 Phenytoin was administered intravenously to six adult epileptic patients in doses ranging from 500-1000 mg (equivalent to 5.6 mg/kg-20 mg/kg body weight). 2 A significant decrease in the frequency of inter-ictal spikes in the EEG was seen and this effect was most marked 10-20 min after the infusion, when the mean spike count was reduced to 27% (s.d. 17%) of the control (P < 0.05). 3 In one subject the decrease in inter-ictal spikes coincided with a decrease in fit frequency. 4 Adverse reactions affecting the vestibular system occurred in three patients at doses of 15-20 mg/kg. No cardiovascular complications were observed in any subject. 5 The overall results suggest that doses of 7.5-10 mg/kg would be sufficient to significantly reduce the frequency of inter-ictal spikes in the EEG.

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Section: Introductionmentioning

confidence: 99%

Acute effects of intravenous phenytoin on the frequency of inter‐ictal spikes in man.

Milligan¹,

Oxley²,

Richens³

1983

Brit J Clinical Pharma

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“…Plasma levels of diazepam, following I .v. administration, approach 10 pkf (Booker andCe'lesia 1973: I-Iillestad eta/. 1974) and brain levels can be sign~ticantly higher (Garattini et a / .…”

Section: )Iscussionmentioning

confidence: 99%

The actions of diazepam and diphenylhydantoin on fast and slow Ca²⁺ uptake processes in guinea pig cerebral cortex synaptosomes

Rampe¹,

Ferrante²,

Triggle³

1987

Can. J. Physiol. Pharmacol.

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The activities of diazepam and diphenylhydantoin as inhibitors of the fast and slow phases of 45Ca2+ uptake in response to K+ depolarization and of [3H]nitrendipine binding were examined in guinea pig cerebral cortex synaptosomes. The slow phase of 45Ca2+ uptake was abolished in Na+-free media (choline substitution) and was more sensitive to inhibition by 3,4-dichlorobenzamil and represents a Na+-dependent Ca2+ uptake process. The fast component of uptake represents activation of voltage-dependent Ca2+ channels. Diazepam (to 300 microM) was selectively active against the fast component of 45Ca2+ uptake. The benzodiazepines Ro 11-3624 and Ro 11-3128 were similarly selective with a modest stereoselectivity against the fast component of 45Ca2+ uptake. Diphenylhydantoin (100 and 200 microM) blocked nonselectively both fast and slow phases of Ca2+ uptake. Diazepam (60 microM) and diphenylhydantoin (200 microM) blocked [3H]nitrendipine binding in a competitive manner. Diazepam and diphenylhydantoin probably exert at least part of their anticonvulsant activity by inhibition of voltage-dependent Ca2+ channels.

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“…Subsequently, Booker & Celesia (1973) counting the total number of EEG spikes over periods of 10 min and expressing the results as the percentage change with respect to the pre-injection period. Diazepam (5 mg), given intravenously over a period of 1 min, provided a valuable reference as it consistently produced a marked degree of reduction of interictal discharges.…”

Section: Discussionmentioning

confidence: 99%

“…Although attempts to find a correlation between improvement of interictal EEGs and the efficacy of chronic antiepileptic therapy have proved disappointing, particularly with carbamazepine (Rodin, Rim & Renwick, 1974), the evaluation of the EEG response to single test doses given parenterally may provide an alternative approach. Single intravenous doses of diazepam or clonazepam, both of which are established antiepileptic agents, can reduce or abolish paroxysmal discharges and interictal spikes (Niedermayer, 1970;Booker & Celesia, 1973;Haikkinen, 1973) and a clear relationship between the serum concentration of diazepam and the resulting depression of spike discharges has been demonstrated (Booker & Celesia, 1973).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Frusemide, Mexiletine, (+)‐propranolol and Three Benzodiazepine Drugs on Interictal Spike Discharges in the Electroencephalograms of Epileptic Patients

Ahmad

Perucca

Richens

1977

Brit J Clinical Pharma

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I The effects of single intravenous doses of diazepam, clonazepam, lorazepam, frusemide, mexiletine and (+)-propranolol on the frequency of electroencephalographic (EEG) interictal spike discharges were assessed in three double-blind placebo-controlled trials in fourteen epileptic patients. 2 Diazepam (5 mg) produced a significant mean decrease of spike discharges to about one third of the control frequency. The effect developed rapidly and persisted for the duration of the study (up to 25 min after injection). A larger dose (10 mg) failed to produce a further reduction in the frequency of the spike discharges. 3 Clonazepam (0.5 mg), frusemide (40 mg) and lorazepam (2 mg) appeared to be as effective as diazepam in reducing spike discharges, although the effect of the latter drug seemed to develop with some delay. 4 Mexiletine (100 mg) and (+)-propranolol (50 mg) did not reduce paroxysmal EEG discharges, their effects being not significantly different from that of saline. 5 EEG spike counting after intravenous administration of single test-doses appeared to be both a simple and promising technique for the rapid preliminary evaluation of the clinical efficacy of new antiepileptic drugs.

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Serum Concentrations of Diazepam in Subjects With Epilepsy

Cited by 74 publications

References 5 publications

Acute effects of intravenous phenytoin on the frequency of inter‐ictal spikes in man.

Acute effects of intravenous phenytoin on the frequency of inter‐ictal spikes in man.

The actions of diazepam and diphenylhydantoin on fast and slow Ca²⁺ uptake processes in guinea pig cerebral cortex synaptosomes

The Effect of Frusemide, Mexiletine, (+)‐propranolol and Three Benzodiazepine Drugs on Interictal Spike Discharges in the Electroencephalograms of Epileptic Patients

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Serum Concentrations of Diazepam in Subjects With Epilepsy

Cited by 74 publications

References 5 publications

Acute effects of intravenous phenytoin on the frequency of inter‐ictal spikes in man.

Acute effects of intravenous phenytoin on the frequency of inter‐ictal spikes in man.

The actions of diazepam and diphenylhydantoin on fast and slow Ca2+ uptake processes in guinea pig cerebral cortex synaptosomes

The Effect of Frusemide, Mexiletine, (+)‐propranolol and Three Benzodiazepine Drugs on Interictal Spike Discharges in the Electroencephalograms of Epileptic Patients

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The actions of diazepam and diphenylhydantoin on fast and slow Ca²⁺ uptake processes in guinea pig cerebral cortex synaptosomes