l-838-417 and Pain

l-838-417 has been researched along with Pain* in 2 studies

Other Studies

2 other study(ies) available for l-838-417 and Pain

ArticleYear
Assessment of the effects of NS11394 and L-838417, α2/3 subunit-selective GABA(A) [corrected] receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function.
    Behavioural pharmacology, 2012, Volume: 23, Issue:8

    The aim of the present paper was to study the effects of GABAA receptor-positive modulators (L-838417 and NS11394) showing a preference for α2/3 subunits of the GABAA receptor, in models of pain, anxiety, learning, memory and motor function. These compounds have been suggested to have a favourable therapeutic profile over nonselective compounds such as diazepam. In this study, we tested both compounds for their effects in rat models of formalin-induced pain, spinal nerve-ligation-induced mechanical allodynia, plus maze, open field, rotarod, balance beam walking, contextual fear conditioning and Morris water maze. Both compounds exerted analgesic, but no anxiolytic effects. However, they induced motor side-effects, and learning and memory impairment at similar doses. Therefore, the anxiolytic effect and the lack of side-effects of these compounds, as described in the literature, could not be confirmed in the present study.

    Topics: Allosteric Regulation; Analgesics; Animals; Anxiety; Benzimidazoles; Disease Models, Animal; Dose-Response Relationship, Drug; Fear; Fluorobenzenes; GABA-A Receptor Agonists; Male; Maze Learning; Memory Disorders; Motor Activity; Pain; Rats; Rats, Wistar; Receptors, GABA-A; Triazoles

2012
Reversal of pathological pain through specific spinal GABAA receptor subtypes.
    Nature, 2008, Jan-17, Volume: 451, Issue:7176

    Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss. With the use of GABA(A)-receptor point-mutated knock-in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine-site ligands, we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha2 and/or alpha3 subunits. We show that their selective activation by the non-sedative ('alpha1-sparing') benzodiazepine-site ligand L-838,417 (ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L-838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative-emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics.

    Topics: Analgesics; Animals; Brain; Capsaicin; Chronic Disease; Diazepam; Disease Models, Animal; Fluorobenzenes; Formaldehyde; Ganglia, Spinal; Hot Temperature; Inflammation; Male; Mice; Neurons; Organ Specificity; Pain; Protein Isoforms; Protein Subunits; Rats; Rats, Wistar; Receptors, GABA-A; Spinal Cord; Triazoles

2008