Guvacine

Brain Research, 1977, 136(3):513-522.

Effects of the Areca nut constituents arecaidine and guvacine on the action of GABA in the cat central nervous system.[Reference: WebLink]

METHODS AND RESULTS:
Arecaidine and Guvacine, constituents of the nut of Areca catechu, inhibited the uptake of GABA and β-alanine, but not that of glycine, by slices of cat spinal cord. In cats anaesthetised with pentobarbitone, electrophoretic arecaidine enhanced the inhibitory actions of GABA and β-alanine, but not those of glycine or taurine, on the firing of spinal neurones. Similarly, electrophoretic Guvacine enhanced the inhibition of spinal neurones by GABA but not that by glycine. The uptake of GABA by slices of cat cerebellum was inhibited by arecaidine, and the effect of electrophoretic GABA on the firing of cerebellar Purkinje cells was enhanced by electrophoretic arecaidine.When administered intravenously arecaidine failed to affect synaptic inhibitions considered to be mediated by GABA. Intravenous arecaidine had no effect on either spinal prolonged (presynaptic) inhibition (20 mg/kg), dorsal root potentials (20 mg/kg) or basket cell inhibition of Purkinje cells (250 mg/kg), although topical arecaidine (6.6–10 × 10−3M) blocked this latter inhibition.
CONCLUSIONS:
Large doses of arecaidine (1 g/kg subcutaneous) marginally reduced the lethal effects of bicuculline in mice but appeared to have little or no anticonvulsant activity.

ChemMedChem. 2019 Jun 18;14(12):1135-1151.

Synthesis and Biological Evaluation of Nipecotic Acid and Guvacine Derived 1,3-Disubstituted Allenes as Inhibitors of Murine GABA Transporter mGAT1.[Pubmed: 30957949]

A new class of nipecotic acid and Guvacine derivatives has been synthesized and characterized for their inhibitory potency at mGAT1-4 and binding affinity for mGAT1.
METHODS AND RESULTS:
Compounds of the described class are defined by a four-carbon-atom allenyl spacer connecting the nitrogen atom of the nipecotic acid or Guvacine head with an aromatic residue. Among the compounds investigated, the mixture of nipecotic acid derivatives rac-{(Ra )-1-[4-([1,1':2',1''-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} and rac-{(Sa )-1-[4-([1,1':2',1''-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} (21 p), possessing an o-terphenyl residue, was identified as highly selective and the most potent mGAT1 inhibitor in this study. For the (R)-nipecotic acid derived form of 21 p, the inhibitory potency in [3 H]GABA uptake assays was determined as pIC50 =6.78±0.08, and the binding affinity in MS Binding Assays as pKi =7.10±0.12.
CONCLUSIONS:
The synthesis of the designed compounds was carried out by a two-step procedure, generating the allene moiety via allenylation of terminal alkynes which allows broad variation of the terminal phenyl and biphenyl subunit.