Gabapentin inhibits calcium currents in isolated rat brain neurons

Stefani, Alessandro; Spadoni, Francesca; Bernardi, Giorgio

doi:10.1016/s0028-3908(97)00189-5

Cited by 189 publications

(95 citation statements)

References 45 publications

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“…Numerous studies have examined the effects of gabapentin or pregabalin on voltage-gated calcium channel function. There are several reports that the drugs reduce calcium current in neuronal cell body membranes (Stefani et al, 1998;Martin et al, 2003;McClelland et al, 2004). However, in other studies with neurons (van Hooft et al, 2002) or recombinant systems (Canti et al, 2003), gabapentin was inactive.…”

mentioning

confidence: 99%

New horizons in the development of antiepileptic drugs: Innovative strategies

Löscher¹,

Schmidt²

2006

Epilepsy Research

104

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confidence: 99%

New horizons in the development of antiepileptic drugs: Innovative strategies

Löscher¹,

Schmidt²

2006

Epilepsy Research

104

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“…GBP exerts effects on the extrinsic properties of neurons (i.e., on different neurotransmitter systems at the presynaptic and the postsynaptic site), as well as on the intrinsic properties (e.g., on voltage-dependent ionic channels) (for review, see (5,6). GBP binds to the ␣ 2 ␦ subunit of voltage-gated calcium channels and may thereby induce an inhibition of calcium currents (7)(8)(9)(10)(11)(12), but see 13). Recently GBP also was suggested to act as a K ATP channel agonist (14).…”

mentioning

confidence: 99%

Gabapentin Increases the Hyperpolarization‐activated Cation Current I_h in Rat CA1 Pyramidal Cells

Surges¹,

Freiman

Feuerstein³

2003

Epilepsia

115

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Summary:Purpose: Gabapentin (GBP) is a commonly used drug in the treatment of partial seizures, but its mode of action is still unclear. The genesis of seizures in temporal lobe epilepsy is thought to be crucially influenced by intrinsic membrane properties. Because the I h substantially contributes to the intrinsic membrane properties of neurons, the effects of GBP on the I h were investigated in CA1 pyramidal cells of rat hippocampus.Methods: CA1 pyramidal cells in hippocampal slices were examined by using the whole-cell patch-clamp technique.Results: GBP increased the I h amplitude in a concentrationdependent manner mainly by increasing the conductance, without significant changes in the activation properties or in the time course of I h . The effects ranged from ∼20% at 50 M, ∼25% at 75 M, to ∼35% at 100 M GBP (at -110 mV). In the presence of intracellular cyclic adenosine monophosphate (cAMP), the effects of GBP on I h were similar to those obtained in the absence of cAMP.Conclusions: These results suggest that GBP increases the I h through a cAMP-independent mechanism. Because the applied GBP concentrations were in a clinically relevant range, the observed effect may contribute to the anticonvulsant action of GBP in partial seizures and may represent a new concept of how this anticonvulsant drug works.

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“…On the other hand, VD-CCs, predominately the L-type channel is proposed as a direct target of gabapentin, as it inhibits L-type calcium currents [76]. …”

Section: Coherence In Toxicokinetic and Molecular-level Evidencementioning

confidence: 99%

The mechanisms of sudden-onset type adverse reactions to oseltamivir

Hama¹,

Bennett

2016

Acta Neurol Scand

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Oseltamivir is contraindicated for people aged 10 to 19 in principle in Japan, due to concern about abnormal behaviours. Sudden death is another concern. This review examines growing evidence of their association and discusses underlying mechanisms of these sudden-onset type reactions to oseltamivir. First the importance of animal models and the concept of human equivalent dose (HED) is summarised. Second, the specific condition for oseltamivir use: influenza infection, is reviewed. Third, findings from toxicity studies conducted prior to and after the marketing of oseltamivir are reported on to provide context on the observation of a possible causal association. Fourth, similarity and consistency of toxicity in humans with that in other animals is described. Finally, coherence of toxicokinetic and molecular-level of evidence (channels, receptors, and enzymes), including differences from the toxicity of other neuraminidase inhibitors, is reviewed. It is concluded that unchanged oseltamivir has various effects on the central nervous system (CNS) that may be related to clinical findings including hypothermia, abnormal behaviours including with fatal outcome, and sudden death. Among receptors and enzymes related to CNS action, it is known that oseltamivir inhibits nicotinic acetylcholine receptors, which are closely related to hypothermia, as well as human monoamine oxidase-A (MAO-A), which is closely related to abnormal or excitatory behaviours. Receptors such as GABAA, GABAB, and NMDA and their related receptors/channels including Na+ and Ca2+ channels are thought to be other candidates for investigation related to respiratory suppression followed by sudden death and psychotic reactions (both acute and chronic) respectively.

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Gabapentin inhibits calcium currents in isolated rat brain neurons

Cited by 189 publications

References 45 publications

New horizons in the development of antiepileptic drugs: Innovative strategies

New horizons in the development of antiepileptic drugs: Innovative strategies

Gabapentin Increases the Hyperpolarization‐activated Cation Current I_h in Rat CA1 Pyramidal Cells

The mechanisms of sudden-onset type adverse reactions to oseltamivir

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Gabapentin inhibits calcium currents in isolated rat brain neurons

Cited by 189 publications

References 45 publications

New horizons in the development of antiepileptic drugs: Innovative strategies

New horizons in the development of antiepileptic drugs: Innovative strategies

Gabapentin Increases the Hyperpolarization‐activated Cation Current Ih in Rat CA1 Pyramidal Cells

The mechanisms of sudden-onset type adverse reactions to oseltamivir

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Gabapentin Increases the Hyperpolarization‐activated Cation Current I_h in Rat CA1 Pyramidal Cells