Analgesic Properties of the Novel Amino Acid, Isovaline

@article{MacLeod2010AnalgesicPO,
  title={Analgesic Properties of the Novel Amino Acid, Isovaline},
  author={Bernard A. MacLeod and Jimmy T. C. Wang and Cheryl C W Chung and Craig R. Ries and Stephan K. W. Schwarz and Ernest Puil},
  journal={Anesthesia \& Analgesia},
  year={2010},
  volume={110},
  pages={1206–1214}
}
BACKGROUND:Isovaline, a nonproteinogenic &agr;-amino acid rarely found in the biosphere, is structurally similar to the inhibitory neurotransmitters glycine and &ggr;-aminobutyric acid. Because glycineA and &ggr;-aminobutyric acid receptor agonists are antiallodynic, we hypothesized that isovaline produces antinociception in mice. METHODS:All experiments were performed on female CD-1 mice using a blinded, randomized, and controlled design. The effects of RS-isovaline were studied on nociceptive… 

Figures from this paper

R-isovaline: a subtype-specific agonist at GABAB-receptors?
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.
Isovaline: A unique amino acid with antiepileptic drug properties
TLDR
The latest published findings which demonstrate the efficacy of isovaline in an in vivo rat model of epilepsy are discussed, which is a clear need to develop new AEDs that may work via novel mechanisms to provide greater efficacy.
GABAB receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline
The Efficacy and Safety of the Novel Peripheral Analgesic Isovaline as an Adjuvant to Propofol for General Anesthesia and Conscious Sedation: A Proof-of-Principle Study in Mice
TLDR
The novel analgesic, isovaline, coadministered with propofol, produced general anesthesia and conscious sedation in mice and provides proof of the principle of combining a peripheral analgesic with a centrally acting hypnotic to produce general anesthesia.
Lumbar Intrathecal Administration of the Quaternary Lidocaine Derivative, QX-314, Produces Irritation and Death in Mice
TLDR
It is indicated that QX-314 is unlikely to be a suitable candidate for spinal anesthesia in humans because of its long-lasting neural blockade, and at lower concentrations than those associated with robust motor blockade.
...
...

References

SHOWING 1-10 OF 44 REFERENCES
Hyperalgesia during sedation: effects of barbiturates and propofol in the rat
TLDR
The hypothesis that hyperalgesia is a property of different anaesthetic agents when administered at sub- hynotic concentrations is tested and supports the hypothesis that barbiturate and non-barbiturate anaesthetic Agents have antianalgesic properties.
Similar effects of acetylsalicylic acid and morphine on immediate responses to acute noxious stimulation.
  • S. Hunskaar
  • Biology, Medicine
    Pharmacology & toxicology
  • 1987
TLDR
No delay of onset in the action of ASA compared to morphine could be demonstrated, and ASA seems to be antinociceptive also in acute non-inflammatory pain.
Coadministration of intrathecal strychnine and bicuculline effects synergistic allodynia in the rat: an isobolographic analysis.
TLDR
The results of this study indicate that glycine and GABA effect cooperative inhibition of low-threshold mechanical input in the spinal cord of the rat; and BIC-allodynia arises from the blockade of GABA(A) receptors and is unrelated to any secondary anticholinesterase activity.
International Union of Pharmacology. XXXIII. Mammalian γ-Aminobutyric AcidB Receptors: Structure and Function
TLDR
The emergence of high-affinity antagonists for GABAB receptors has enabled a synaptic role to be established, however, the antagonists have generally failed to establish the existence of pharmacologically distinct receptor types within the GABAB receptor class.
Strychnine-dependent allodynia in the urethane-anesthetized rat is segmentally distributed and prevented by intrathecal glycine and betaine.
TLDR
The hypothesis that removal of spinal glycinergic modulation from low threshold afferent input with intrathecal strychnine results in segmentally localized, tactile-evoked allodynia is supported.
Phencyclidine analogs and precursors: rotarod and lethal dose studies in the mouse.
TLDR
The precursors of PCP failed to elicit the stereotyped movements and hyperactivity that preceded seizures produced by the other compounds, and overall potencies for lethality relative to PCP covered a narrow range with the carbonitrile precursor being most potent.
Glycine Inhibitory Dysfunction Induces a Selectively Dynamic, Morphine-Resistant, and Neurokinin 1 Receptor- Independent Mechanical Allodynia
TLDR
The present findings reveal the involvement of a selective dorsal horn circuit in dynamic mechanical allodynia, which operates through superficial lamina nociceptive-specific neurons that do not bear NK1 receptor and provide an explanation for the differences in the pharmacological sensitivity of neuropathic pain symptoms.
α2δ and the mechanism of action of gabapentin in the treatment of pain
...
...