Benzodiazepines Used in the Treatment of Epilepsy

Trinka, Eugen; Brigo, Francesco

doi:10.1002/9781118936979.ch30

Cited by 6 publications

(8 citation statements)

References 235 publications

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“…Some BDZ (diazepam, lorazepam, clonazepam, clobazam, and midazolam) have also anticonvulsant effects. The first benzodiazepine was discovered serendipitously and marketed in 1957; since then, these drugs have been widely prescribed and increasingly used in clinical practice to treat anxiety, insomnia, and seizures (Trinka and Brigo 2015).…”

Section: Chemistry Developmental Historymentioning

confidence: 99%

“…Benzodiazepines are rapidly and extensively absorbed from the gastrointestinal tract, usually reaching peak serum concentrations in less than 4 h after a single oral dose (Trinka and Brigo 2015). The oral bioavailability of clobazam, clonazepam, diazepam, lorazepam, and midazolam is almost complete.…”

Section: Pharmacology Pharmacokineticsmentioning

confidence: 99%

“…Benzodiazepines are eliminated almost entirely by hepatic metabolism involving cytochrome P450 enzymes (CYP2C19 and CYP3A4) and glucuronyltransferase. Some metabolites (e.g., N-desmethylclobazam, the product of hepatic metabolism of clobazam) also have antiepileptic properties (Trinka and Brigo 2015).…”

Section: Pharmacology Pharmacokineticsmentioning

confidence: 99%

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Anticonvulsant Agents: Benzodiazepines (Clobazam, Clonazepam, Diazepam, Lorazepam, Midazolam)

Brigo¹,

Lattanzi²

2020

NeuroPsychopharmacotherapy

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Clobazam, clonazepam, diazepam, lorazepam, and midazolam are benzodiazepines with antiseizure activity. They act by increasing the opening frequency of gamma-aminobutyric acid-activated chloride channels resulting in enhanced inhibitory neurotransmission. The duration of the antiepileptic effect depends on their half-life, rate of absorption, and lipophilicity. The concomitant administration of enzyme-inducing or inhibiting drugs can modify the metabolism of benzodiazepines. Their most common side effects are systemic adverse effects

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Section: Chemistry Developmental Historymentioning

confidence: 99%

Section: Pharmacology Pharmacokineticsmentioning

confidence: 99%

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Anticonvulsant Agents: Benzodiazepines (Clobazam, Clonazepam, Diazepam, Lorazepam, Midazolam)

Brigo¹,

Lattanzi²

2020

NeuroPsychopharmacotherapy

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“…The US Food and Drug Administration had just approved what would become an important drug milestone in the years to come: diazepam (DZP; first commercially marketed with the brand name of Valium) (1). The drug, belonging to the benzodiazepines (BDZs) class (2), successfully treated insomnia (3)(4)(5), anxiety disorders (6)(7)(8), epilepsy (9)(10)(11), muscle spasms (12), and alcohol withdrawal (13). Although novel and safer medications have been developed over the years, DZP still remains a fundamental treatment option; while the clinical use of the drug has been vastly exploited and, at a certain level, surpassed by better agents, its use in experimental neuropharmacology is still of cardinal importance.…”

mentioning

confidence: 99%

Photopotentiation of the GABA _A receptor with caged diazepam

Sansalone

Bratsch-Prince

Tang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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As the inhibitory γ-aminobutyric acid–ergic (GABAergic) transmission has a pivotal role in the central nervous system (CNS) and defective forms of its synapses are associated with serious neurological disorders, numerous versions of caged GABA and, more recently, photoswitchable ligands have been developed to investigate such transmission. While the complementary nature of these probes is evident, the mechanisms by which the GABA receptors can be photocontrolled have not been fully exploited. In fact, the ultimate need for specificity is critical for the proper synaptic exploration. No caged allosteric modulators of the GABAA receptor have been reported so far; to introduce such an investigational approach, we exploited the structural motifs of the benzodiazepinic scaffold to develop a photocaged version of diazepam (CD) that was tested on basolateral amygdala (BLa) pyramidal cells in mouse brain slices. CD is devoid of any intrinsic activity toward the GABAA receptor before irradiation. Importantly, CD is a photoreleasable GABAA receptor-positive allosteric modulator that offers a different probing mechanism compared to caged GABA and photoswitchable ligands. CD potentiates the inhibitory signaling by prolonging the decay time of postsynaptic GABAergic currents upon photoactivation. Additionally, no effect on presynaptic GABA release was recorded. We developed a photochemical technology to individually study the GABAA receptor, which specifically expands the toolbox available to study GABAergic synapses.

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“…Diazepam (DZP), lorazepam (LZP) and midazolam (MDZ) are the most widely used drugs in both adults and children. They have different pharmacokinetic profiles [5,6] and are available in different pharmacological formulations [1,7] (Table 1). For many years, rectal diazepam has been a very popular rescue medication and still represents the only out of hospital treatment approved in the US, but this rout of administration is problematic and most of the time socially unacceptable, especially in adults [8].…”

Section: Introductionmentioning

confidence: 99%

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

Mula

2016

CNS Drugs

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Benzodiazepines (BDZs) represent first line treatment for the acute management of epileptic seizures and status epilepticus. The emergency use of BDZs requires timely administration and considering that most seizures occur outside of the hospital, there is a significant need for easy to use delivery methods that can be given quickly and safely by nonclinical caregivers. In addition, the ideal route of administration should be reliable in terms of absorption. In the US, rectal diazepam is the only licensed formulation, while in the EU rectal diazepam and buccal midazolam are currently licensed. However, both the rectal and buccal administration are not ideal as the absorption can be sometimes unpredictable. Several alternative routes are being explored and are currently under investigation. This is a narrative review of available data about delivery methods for BDZs alternative to the intravenous and oral routes for the acute treatment of seizures. Unconventional delivery options such as the direct delivery in the central nervous system or inhalers are reported. Available data shows that intranasal diazepam or midazolam and the intramuscular auto-injector for midazolam are as effective as rectal or intravenous diazepam. Head to head comparisons with buccal midazolam are urgently needed. In addition, the majority of trials focused on children and adolescents and further trials in adults are warranted.

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Benzodiazepines Used in the Treatment of Epilepsy

Cited by 6 publications

References 235 publications

Anticonvulsant Agents: Benzodiazepines (Clobazam, Clonazepam, Diazepam, Lorazepam, Midazolam)

Anticonvulsant Agents: Benzodiazepines (Clobazam, Clonazepam, Diazepam, Lorazepam, Midazolam)

Photopotentiation of the GABA _A receptor with caged diazepam

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

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Benzodiazepines Used in the Treatment of Epilepsy

Cited by 6 publications

References 235 publications

Anticonvulsant Agents: Benzodiazepines (Clobazam, Clonazepam, Diazepam, Lorazepam, Midazolam)

Anticonvulsant Agents: Benzodiazepines (Clobazam, Clonazepam, Diazepam, Lorazepam, Midazolam)

Photopotentiation of the GABA A receptor with caged diazepam

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

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Product

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Photopotentiation of the GABA _A receptor with caged diazepam