GABAB receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline

@article{Whitehead2012GABABRS,
  title={GABAB receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline},
  author={Ryan A. Whitehead and Ernest Puil and Craig R. Ries and Stephan K. W. Schwarz and Richard A. Wall and James E. Cooke and Igor Putrenko and Nada A. Sallam and Bernard A. MacLeod},
  journal={Neuroscience},
  year={2012},
  volume={213},
  pages={154-160}
}
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37 Citations
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37 Citations

Group II metabotropic glutamate receptor antagonism prevents the antiallodynic effects of R-isovaline
Activation and modulation of GABA(B) receptor systems in physiogenic and pathophysiological conditions
TLDR
The abilities of baclofen and the D2 agonist quinpirole to inhibit dopamine release were unchanged by long term access to a palatable cafeteria diet and the data suggest that R-isovaline does not act as a direct agonist at GABAB receptors.
Differential effects of R-isovaline and the GABAB agonist, baclofen, in the guinea pig ileum.
Targeting the GABA B Receptor for the Treatment of Pain
TLDR
The neuroanatomical localization and function of GABAergic neurons as they relate to nociception and to the antinociceptive responses to GABAB receptor agonists are described and strategies are described for developing GABAergic drugs that by selectively activating sites associated with pain pathways provoke fewer side effects and less tolerance than orthosteric agents.
Isovaline Does Not Activate GABAB Receptor-Coupled Potassium Currents in GABAB Expressing AtT-20 Cells and Cultured Rat Hippocampal Neurons
TLDR
R-isovaline does not interact with recombinant or native GABAB receptors to open K+ channels in cells of recombinant and native receptor preparations, and differs from those of the canonical GABAB receptor agonist R-baclofen.
Systemic and intrathecal baclofen produce bladder antinociception in rats
TLDR
Support is provided for a clinical trial of baclofen as a non-opioid treatment of human bladder pain through dose-dependent inhibition of visceromotor responses to urinary bladder distension (UBD).
Analgesic effect of ADX71441, a positive allosteric modulator (PAM) of GABAB receptor in a rat model of bladder pain
GABA Pharmacology: The Search for Analgesics
TLDR
It is demonstrated that at least some types of persistent pain are associated with a regionally selective decline in GABAergic tone, highlighting the need for agents that enhance GABA activity in the affected regions without compromising GABA function over the long-term.
Antinociceptive Effects of H3 (R-Methylhistamine) and GABAB (Baclofen)-Receptor Ligands in an Orofacial Model of Pain in Rats
TLDR
It is demonstrated that GABAB receptors represent peripheral targets for analgesia and locally administered baclofen may be a useful approach in treating inflammatory trigeminal pain.
Variations of isovaline structure related to activity in the formalin foot assay in mice
TLDR
Findings indicate that the conformational stability of isovaline or the ability to form a cyclobutane ring is necessary for activity in the formalin foot assay.
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References

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