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Cited by 135Neuroprotection in Cerebral IschemiaNerve injury and regenerationPharmacological Receptor Mechanisms and Effects

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

SSR180575 (7-Chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4 H-pyridazino[4,5-b]indole-1-acetamide), a Peripheral Benzodiazepine Receptor Ligand, Promotes Neuronal Survival and Repair

Ferzaz, Badia, Brault, Emmanuel, Bourliaud, Genevieve, Robert, Jean-Pierre, Poughon, Gilles, Claustre, Yves, Marguet, Franck, Liere, Philippe, Schumacher, Michael, Nowicki, Jean-Pierre, Fournier, Jacqueline, Marabout, Benoit, Sevrin, Mireille, George, Pascal, Soubrie, Philippe, Benavides, Jesus, Scatton, Bernard·2002·The Journal of Pharmacology and Experimental Therapeutics
DOI 10.1124/jpet.301.3.1067
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Abstract

In the present study, we have investigated the potential neuroprotective effects of a novel peripheral benzodiazepine binding site (PBR) ligand, 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (SSR180575), in models of central and peripheral neurodegeneration in vivo and its effect on steroid concentrations in plasma and nervous tissue. SSR180575 shows high affinity (IC(50), 2.5-3.5 nM) and selectivity for the rat and human PBR and potently inhibits the in vivo binding of [(3)H]alpidem to PBR in the rat brain and spleen after oral or i.p. administration (ID(50), 0.1-0.3 mg/kg). In an experimental model of motoneuron degeneration induced by facial nerve axotomy in the immature rat, SSR180575 given i.p. or orally for 8 days rescued facial motoneurons, increasing their survival by 40 to 72% at 6 and 10 mg/kg p.o. b.i.d. Moreover, in this model, SSR180575 (10 mg/kg p.o. b.i.d.) increased by 87% the number of motoneurons immunoreactive to peripherin, a type III intermediate filament, whose expression is up-regulated during nerve regeneration. SSR180575 also improved functional recovery in acrylamide-induced neuropathy in the rat when given therapeutically at 2.5 to 10 mg/kg/day p.o. Furthermore, SSR180575 (3 mg/kg i.p. b.i.d.) accelerated functional recovery of the blink reflex after local injury of the facial nerve in the rat. SSR180575 increased pregnenolone accumulation in the brain and sciatic nerve (+100% at 3 mg/kg i.p.), suggesting…

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Metadata

Authors
Ferzaz, B., Brault, E., Bourliaud, G., Robert, J.-P., Poughon, G., Claustre, Y., Marguet, F., Liere, P., Schumacher, M., Nowicki, J.-P., Fournier, J., Marabout, B., Sevrin, M., George, P., Soubrie, P., Benavides, J., & Scatton, B.
Affiliations
Sanofi (France) (FR)
ORCID
Scatton, Bernard
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
2002-06
Volume
301
Issue
3
Pages
1067-1078
ISSN
0022-3565 (ISSN-L)
DOI
10.1124/jpet.301.3.1067
OpenAlex
W2155301275
Cited by
126
References
41
Citations by year
2024: 5 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 4 · 2017: 7 · 2016: 11 · 2015: 3 · 2014: 4 · 2013: 6 · 2012: 3
FWCI
5.38
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
Keywords
translocator protein (TSPO), neuroprotection, motor neuron degeneration, facial nerve axotomy, pregnenolone, peripherin, nerve regeneration, functional recovery, blink reflex
MeSH terms
Acetamides, Aging, Animals, Binding, Competitive, Cell Survival, Facial Nerve, Humans, Imidazoles, Indoles, Ligands, Male, Motor Neurons, Pyridazines, Pyridines, Receptors, GABA-A, Anti-Anxiety Agents, Rats, Sprague-Dawley, Neuroprotective Agents, Axotomy, Rats, GABA-A Receptor Agonists, GABA-A Receptor Antagonists

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