A double blind parallel group placebo controlled comparison of sedative and amnesic effects of etifoxine and lorazepam in healthy subjects

Micallef, Joëlle; Soubrouillard, C; Guet, F.; Guern, Monique; Alquier, Christine; Bruguerolle, Bernard; Blin, Olivier

doi:10.1046/j.1472-8206.2001.00025.x

Cited by 59 publications

(30 citation statements)

References 29 publications

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“…An impact of lorazepam on CPT performance has been expected from known effects of lorazepam, as well as from earlier studies (Duka et al, 1995;Fluck et al, 2001;Kathmann et al, 1996;Krystal et al, 1998;Mass et al, 2000;Micallef et al, 2001;Post et al, 1997). The data illustrate that the performance in controlled visual attention was clearly impaired by lorazepam intake.…”

Section: Cpt Performancesupporting

confidence: 49%

“…Besides that, on the behavioral level an attenuation of attention performance with benzodiazepines is well documented (Duka et al, 1995;Fluck et al, 2001;Krystal et al, 1998;Micallef et al, 2001;Post et al, 1997). However, since attention can be regarded as a process of information and response selection, pure behavioral studies can hardly reveal which levels of information processing are affected by benzodiazepines.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Lorazepam on the Neuromagnetic Mismatch Negativity (MMNm) and Auditory Evoked Field Component N100m

Rosburg

Marinou

Haueisen

et al. 2004

Neuropsychopharmacol

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The mismatch negativity (MMN) as an auditory evoked potential is thought to reflect an early, preconscious attention process. While this component has gained great importance in studies on clinical populations and in basic research on auditory information processing, the involvement of different neurotransmitters in the generation of this component is less well understood. We investigated the impact of the benzodiazepine lorazepam as a GABA agonist on the neuromagnetic MMN (MMNm) and auditory evoked field component N100m. A group of 12 healthy subjects was studied in single blind trials under the following three conditions: after the intake of 1.25 mg lorazepam, 100 mg caffeine or placebo. Neuromagnetic recordings were obtained before drug intake and three times after it. Controlled visual attention was tested additionally using a version of the Continuous Performance Test (CPT). The neuromagnetic activity was reconstructed by a single moving dipole, and the dipole moment and its latency were compared between conditions and time points of measurement. Lorazepam diminished the signal detection performance in the CPT 25 min after drug intake. The source of the field component N100m was attenuated, most significantly in the recording 105 min after lorazepam intake. The attenuation of the MMNm under lorazepam became significant at 105 min, but was visually less apparent, because in all conditions a decrease of the MMNm dipole moment within the course of a session was observed. Besides the already known effects of benzodiazepines on controlled attention functions, preconscious attention functions as reflected in the MMN are impaired by acute benzodiazepine intake. MMN studies on clinical populations have to be controlled for the recording time because of the strong habituation of this component.

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Section: Cpt Performancesupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Effects of Lorazepam on the Neuromagnetic Mismatch Negativity (MMNm) and Auditory Evoked Field Component N100m

Rosburg

Marinou

Haueisen

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

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“…Moreover, the drug is already efficiently used in long-duration (up to 3 months) treatment of adjustment disorders with anxiety, and it is devoid of many of the side effects linked to benzodiazepine anxiolytics (35)(36)(37). This is important, given that axonal regeneration after injury and in peripheral neuropathies is a slow process, and only molecules that can be administered over sufficient periods would be expected to have therapeutic benefits.…”

Section: Discussionmentioning

confidence: 99%

Etifoxine improves peripheral nerve regeneration and functional recovery

Girard

Liu

Cadepond

et al. 2008

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

140

112

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Peripheral nerves show spontaneous regenerative responses, but recovery after injury or peripheral neuropathies (toxic, diabetic, or chronic inflammatory demyelinating polyneuropathy syndromes) is slow and often incomplete, and at present no efficient treatment is available. Using well-defined peripheral nerve lesion paradigms, we assessed the therapeutic usefulness of etifoxine, recently identified as a ligand of the translocator protein (18 kDa) (TSPO), to promote axonal regeneration, modulate inflammatory responses, and improve functional recovery. We found by histologic analysis that etifoxine therapy promoted the regeneration of axons in and downstream of the lesion after freeze injury and increased axonal growth into a silicone guide tube by a factor of 2 after nerve transection. Etifoxine also stimulated neurite outgrowth in PC12 cells, and the effect was even stronger than for specific TSPO ligands. Etifoxine treatment caused a marked reduction in the number of macrophages after cryolesion within the nerve stumps, which was rapid in the proximal and delayed in the distal nerve stumps. Functional tests revealed accelerated and improved recovery of locomotion, motor coordination, and sensory functions in response to etifoxine. This work demonstrates that etifoxine, a clinically approved drug already used for the treatment of anxiety disorders, is remarkably efficient in promoting acceleration of peripheral nerve regeneration and functional recovery. Its possible mechanism of action is discussed, with reference to the neurosteroid concept. This molecule, which easily enters nerve tissues and regulates multiple functions in a concerted manner, offers promise for the treatment of peripheral nerve injuries and axonal neuropathies.inflammation ͉ macrophage ͉ axonal growth ͉ Translocator Protein (18 kDa)

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“…Etifoxine fulfills the criteria of a drug that is clinically useful for the treatment of altered peripheral axons: i) easy diffusion into nerve tissues; ii) selective modulation of inflammatory responses to injury; iii) able to increase the expression of neurotrophic factors; iv) suitable for long-term use (52,53) and (v) convenient administration. Considering the important benefits of etifoxine, etifoxine treatment may represent a promising strategy for the treatment of peripheral nerve injury.…”

Section: Discussionmentioning

confidence: 99%

Etifoxine promotes glial-derived neurotrophic factor-induced neurite outgrowth in PC12 cells

Zhou

et al. 2013

Molecular Medicine Reports

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Abstract. Nerve regeneration and functional recovery are major issues following nerve tissue damage. Etifoxine is currently under investigation as a therapeutic strategy for promoting neuroprotection, accelerating axonal regeneration and modulating inflammation. In the present study, a well-defined PC12 cell model was used to explore the underlying mechanism of etifoxine-stimulated neurite outgrowth. Etifoxine was found to promote glial-derived growth factor (GDNF)-induced neurite outgrowth in PC12 cells. Average axon length increased from 50.29±9.73 to 22.46±5.62 µm with the use of etifoxine. However, blockage of GDNF downstream signaling was found to lead to the loss of this phenomenon. The average axon length of the etifoxine group reduces to a normal level after the blockage of the GDNF family receptor α1 (GFRα1) and receptor tyrosine kinase (RETS) receptors (27.46 ± 3.59 vs. 22.46 ± 5.62 µm and 25.31±3.68 µm vs. 22.46±5.62 µm, respectively, p>0.05). In addition, etifoxine markedly increased GDNF mRNA and protein expression (1.55-and 1.36-fold, respectively). However, blockage was not found to downregulate GDNF expression. The results of the current study demonstrated that etifoxine stimulated neurite outgrowth via GDNF, indicating that GDNF represents a key molecule in etifoxine-stimulated neurite outgrowth in PC12 cells. IntroductionTraumatic injury to peripheral nerves results in considerable loss of sensory and motor function, decreasing quality of life in patients (1). Peripheral nerve injuries substantially impact quality of life through loss of function and increased risk of secondary disabilities from falls, fractures and other injuries. Several research groups have attempted to improve the regeneration of traumatized nerves by developing favorable microsurgical techniques. However, clinicians soon noted that despite advancement in these techniques, complete recovery is rarely achieved (2,3). Therefore, complete recovery remains an important clinical challenge for the improvement of functional recovery following peripheral nerve injury. In a discussion of future trends in the management of brachial plexus injuries, Birch hypothesized that the administration of nerve growth factor may represent a useful treatment strategy (4).Neurotrophic factors are important in a number of biological processes, including survival, proliferation, differentiation and apoptosis of neurons in the nervous system (5-7). However, direct use of trophic factors in clinical practice is extremely challenging as they are difficult to administer and have severe side effects (8). However, molecules that easily diffuse into nerve tissues, including ligands of the progesterone and thyroid hormone receptors, and immunophilins, have beneficial effects on peripheral nerves in various experimental lesion and disease models (9-12). We hypothesize that clinically established drugs may be suitable to elevate trophic factor levels to improve the outcome of peripheral nerve injuries.Previous studies have demonstrated that the drug, etifoxi...

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A double blind parallel group placebo controlled comparison of sedative and amnesic effects of etifoxine and lorazepam in healthy subjects

Cited by 59 publications

References 29 publications

Effects of Lorazepam on the Neuromagnetic Mismatch Negativity (MMNm) and Auditory Evoked Field Component N100m

Effects of Lorazepam on the Neuromagnetic Mismatch Negativity (MMNm) and Auditory Evoked Field Component N100m

Etifoxine improves peripheral nerve regeneration and functional recovery

Etifoxine promotes glial-derived neurotrophic factor-induced neurite outgrowth in PC12 cells

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