Synthesis and in vitro studies on a potential dopamine prodrug

Libero Italo Giannola, Liliana Lamartina, Viviana De Caro, Giulia Giandalia, Maria Gabriella Siragusa

Risultato della ricerca: Articlepeer review

12 Citazioni (Scopus)

Abstract

Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of blood-brain barrier (BBB) which is a selective interface that excludes most water-soluble molecules from entering the brain. Neutral amino acids permeate the BBB by specific transport systems. Conden- sation of dopamine with neutral amino acids could afford potential prodrugs able to interact with the BBB endogenous transporters and easily enter the brain. The synthesis and characterization of the dopamine derivative 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (7) is de- scribed. The chemical and enzymatic stability of 7 was evaluated. The molecular weight (300 Da) and Log P app (0.76) indicated that the physico-chemical characteristics of compound 7 are adequate to cross biological membranes. Compound 7 was enzymatically cleaved to free dopamine in rat brain homogenate (t 1/2 ¼ 460 min). In human plasma, the t 1/2 of 7 was estimated comparable to that re- ported for l -DOPA. In view of a possible oral administration of 7, studies of its chemical behavior under conditions simulating those of the gastrointestinal tract showed that no dopamine production occurred; furthermore, 7 is able to permeate through a simulated intestinal mucosal membrane. The collected data suggest that compound 7 could be considered a very valuable candidate for subse- quent in vivo evaluation.
Lingua originaleEnglish
pagine (da-a)704-710
Numero di pagine7
RivistaPHARMAZIE
Volume63
Stato di pubblicazionePublished - 2008

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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