Novel codrugs with GABAergic activity for dopamine delivery in the brain

Nunzio Denora, Tommaso Cassano, Valentino Laquintana, Antonio Lopalco, Adriana Trapani, Concetta Stefania Cimmino, Leonardo Laconca, Andrea Giuffrida, Giuseppe Trapani

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


This study investigates the use of codrugs of the GABAergic agent 2-phenyl-imidazo[1,2-a]pyridinacetamide and dopamine (DA) or ethyl ester L-Dopa (LD) as a strategy to deliver DA and simultaneously activate GABA-receptors in the brain. For this purpose, both DA and LD ethyl ester were linked by carbamate bond to imidazo[1,2-a]pyridine acetamide moieties to yield two DA- and two LD-imidazopyridine derivatives. These compounds were evaluated in vitro to assess their stability, binding affinities and cell membrane transport, and in vivo to assess their bio-availability via microdialysis studies. The two DA derivatives were adequately stable in buffered solution, but underwent cleavage in diluted human serum. By contrast, the LD derivatives were unstable in buffered solution. Receptor binding studies showed that the DA-imidazopyridine carbamates had binding affinity for benzodiazepine receptors in the nanomolar range. Brain microdialysis experiments indicated that intraperitoneal administration of the DA derivatives sustained DA levels in rat striatum over a 4-h period. These results suggest that DA-imidazopyridine carbamates are new DA codrugs with potential application for DA replacement therapy.

Original languageEnglish (US)
Pages (from-to)221-231
Number of pages11
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - Nov 1 2012


  • Blood-brain barrier
  • Codrugs
  • Drug targeting
  • MDCKII-MDR1 cell
  • Microdialysis
  • P-glycoprotein

ASJC Scopus subject areas

  • Pharmaceutical Science


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