Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential?

Garratt, Jeni C.; Gent, J P; Feely, M.; Haigh, J. R. M.

doi:10.1016/0014-2999(88)90351-2

Cited by 32 publications

(5 citation statements)

References 19 publications

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“…Studies on GABA-induced membrane conductance in cultured spinal neurones demonstrated that some of the conventional BZDs such as clonazepam and chlorodiazepoxide might have partial agonist properties and this would correlate with the longer duration of treatment required with these two compounds to induce anticonvulsant tolerance (Gent et al, 1985;Garratt et al, 1988). No development of tolerance as well as lack of receptor down regulation and decrease in GABAA receptor function after chronic administration with partial BZD agonists have been repeatedly reported (Boast & Gerhardt, 1987;Haigh & Feely, 1988b;Feely et al, 1989;Miller et al, 1990).…”

Section: Discussionmentioning

confidence: 96%

Lack of anticonvulsant tolerance and benzodiazepine receptor down regulation with imidazenil in rats

Zanotti¹,

Mariot²,

Contarino³

et al. 1996

British J Pharmacology

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1 Development of anticonvulsant tolerance and benzodiazepine (BZD) receptor down-regulation has been reported to occur upon chronic administration of conventional BZDs. We compared the effect of chronic treatment with imidazenil, a new BZD partial agonist, and diazepam in rats. 2 After acute administration, imidazenil was more potent though less effective than diazepam in protecting from bicuculline-induced seizure. The time-course analysis of two peak equieffective doses of imidazenil (2.5 yumol kg -' p.o.) and diazepam (35 umol kg-l, p.o.) showed a longer lasting action of the former drug. 7 These data indicate that imidazenil possesses a very low tolerance potential to its anticonvulsant activity and does not affect BZD receptor density even after prolonged administration.

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Section: Discussionmentioning

confidence: 96%

Lack of anticonvulsant tolerance and benzodiazepine receptor down regulation with imidazenil in rats

Zanotti¹,

Mariot²,

Contarino³

et al. 1996

British J Pharmacology

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“…When BZDs are used as anticonvulsants, the time to onset of tolerance varies, and the potential of a BZD to induce anticonvulsant tolerance does not appear to have any relationship with its chemical or pharmacokinetic properties (188). Differences in the development of anticonvulsant tolerance have been reported for various BZDs in an amygdala‐kindling rat model.…”

Section: Tolerance and Withdrawalmentioning

confidence: 99%

Benzodiazepines in epilepsy: pharmacology and pharmacokinetics

Riss

Cloyd

Gates

et al. 2008

Acta Neurologica Scandinavica

430

291

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Benzodiazepines (BZDs) remain important agents in the management of epilepsy. They are drugs of first choice for status epilepticus and seizures associated with post‐anoxic insult and are also frequently used in the treatment of febrile, acute repetitive and alcohol withdrawal seizures. Clinical advantages of these drugs include rapid onset of action, high efficacy rates and minimal toxicity. Benzodiazepines are used in a variety of clinical situations because they have a broad spectrum of clinical activity and can be administered via several routes. Potential shortcomings of BZDs include tolerance, withdrawal symptoms, adverse events, such as cognitive impairment and sedation, and drug interactions. Benzodiazepines differ in their pharmacologic effects and pharmacokinetic profiles, which dictate how the drugs are used. Among the approximately 35 BZDs available, a select few are used for the management of seizures and epilepsy: clobazam, clonazepam, clorazepate, diazepam, lorazepam and midazolam. Among these BZDs, clorazepate has a unique profile that includes a long half‐life of its active metabolite and slow onset of tolerance. Additionally, the pharmacokinetic characteristics of clorazepate (particularly the sustained‐release formulation) could theoretically help minimize adverse events. However, larger, controlled studies of clorazepate are needed to further examine its role in the treatment of patients with epilepsy.

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“…In clinical use, chronic benzodiazepine administration is associated with the development of tolerance to anticonvulsant and hypnotic effects (e.g., Greenblatt & Shader, 1978). Tolerance has also been observed in a number of animal models with a variety of benzodiazepines, including 'classical' benzodiazepines and the newer triazolobenzodiazepines (Garratt et al, 1989). In previous studies, we demonstrated the development of tolerance during chronic administration of the classical benzodiazepine lorazepam (Miller et al, 1988a) and the triazolobenzodiazepine alprazolam (Miller et al, 1989c).…”

Section: Introductionmentioning

confidence: 99%

Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABA_A‐receptor function

Galpern

Miller

Greenblatt

et al. 1990

British J Pharmacology

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Chronic benzodiazepine administration has been associated with tolerance and with downregulation of γ‐aminobutyric acidA (GABAA)‐receptor binding and function. However, effects of individual benzodiazepines on brain regions have varied. To compare the effects of chronic lorazepam and alprazolam, we have administered these drugs to mice for 1 and 7 days (2 mg kg−1 day−1) and determined benzodiazepine receptor binding in vivo with and without administration of CL 218,872, 25 mg kg−1 i.p., and GABA‐dependent chloride uptake in 3 brain regions at these time points. Benzodiazepine binding was decreased in the cortex and hippocampus at day 7 compared to day 1 of lorazepam, with an increase in CL 218,872‐resistant (Type 2) sites in both regions. Maximal GABA‐dependent chloride uptake was also decreased in the cortex and hippocampus at day 7. Binding was decreased only in the cortex after 7 days of alprazolam, with no significant change in Type 2 binding. Maximal GABA‐dependent chloride uptake was also decreased only in the cortex. These data suggest that the effects of chronic benzodiazepine administration on the GABAA‐receptor may be both region‐specific and receptor subtype‐specific.

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Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential?

Cited by 32 publications

References 19 publications

Lack of anticonvulsant tolerance and benzodiazepine receptor down regulation with imidazenil in rats

Lack of anticonvulsant tolerance and benzodiazepine receptor down regulation with imidazenil in rats

Benzodiazepines in epilepsy: pharmacology and pharmacokinetics

Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABA_A‐receptor function

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Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential?

Cited by 32 publications

References 19 publications

Lack of anticonvulsant tolerance and benzodiazepine receptor down regulation with imidazenil in rats

Lack of anticonvulsant tolerance and benzodiazepine receptor down regulation with imidazenil in rats

Benzodiazepines in epilepsy: pharmacology and pharmacokinetics

Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABAA‐receptor function

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Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABA_A‐receptor function