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Maleic- and fumaric-diamides of (O,O-diacetyl)-L-Dopa-methylester as anti-Parkinson prodrugs in liposomal formulation.
J Drug Target. 2006 Nov; 14(9):652-61.JD

Abstract

The maleic and fumaric diamides preparation of (O,O-diacetyl)-L-Dopa-methylester [(+)-4, (+)-5] are reported; they were synthesized in order to attenuate marked fluctuations of L-DOPA (LD) plasma levels and to overcome the problem of low bioavailability of LD. The new compounds were characterized evaluating solubility, chemical stability, apparent partition coefficient (log P) and comparing neostriatum dopamine (DA) levels in freely moving rats after i.p. administration of prodrugs [(+)-4, (+)-5] with prodrugs in liposomal formulations [(+)-4Lip, (+)-5Lip]. All the new compounds showed chemical stability in aqueous buffer solutions (pH 1.3 and 7.4). A relatively slow release of LD in human plasma was observed. Among the studied products, prodrug was able to induce sustained delivery of DA in rat striatal dialysate with respect to equimolar i.p admistration of LD. Furthermore, neostriatum DA concentration after administration of the synthesized prodrugs vs. prodrugs in liposomal formulations was compared (+)-4Lip, (+)-5Lip). The results suggest that cis dimeric prodrug (+)-4 and (+)-4Lip can improve the release of DA in rat brain and demonstrate the potential of these formulations for controlled delivery of antiparkinson agents.

Authors+Show Affiliations

Department of Drug Sciences, School of Pharmacy, "G. d'Annunzio" University, Chieti, Italy. adistefano@unich.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17090401

Citation

Di Stefano, Antonio, et al. "Maleic- and Fumaric-diamides of (O,O-diacetyl)-L-Dopa-methylester as anti-Parkinson Prodrugs in Liposomal Formulation." Journal of Drug Targeting, vol. 14, no. 9, 2006, pp. 652-61.
Di Stefano A, Sozio P, Iannitelli A, et al. Maleic- and fumaric-diamides of (O,O-diacetyl)-L-Dopa-methylester as anti-Parkinson prodrugs in liposomal formulation. J Drug Target. 2006;14(9):652-61.
Di Stefano, A., Sozio, P., Iannitelli, A., Marianecci, C., Santucci, E., & Carafa, M. (2006). Maleic- and fumaric-diamides of (O,O-diacetyl)-L-Dopa-methylester as anti-Parkinson prodrugs in liposomal formulation. Journal of Drug Targeting, 14(9), 652-61.
Di Stefano A, et al. Maleic- and Fumaric-diamides of (O,O-diacetyl)-L-Dopa-methylester as anti-Parkinson Prodrugs in Liposomal Formulation. J Drug Target. 2006;14(9):652-61. PubMed PMID: 17090401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Maleic- and fumaric-diamides of (O,O-diacetyl)-L-Dopa-methylester as anti-Parkinson prodrugs in liposomal formulation. AU - Di Stefano,Antonio, AU - Sozio,Piera, AU - Iannitelli,Antonio, AU - Marianecci,Carlotta, AU - Santucci,Eleonora, AU - Carafa,Maria, PY - 2006/11/9/pubmed PY - 2007/2/7/medline PY - 2006/11/9/entrez SP - 652 EP - 61 JF - Journal of drug targeting JO - J Drug Target VL - 14 IS - 9 N2 - The maleic and fumaric diamides preparation of (O,O-diacetyl)-L-Dopa-methylester [(+)-4, (+)-5] are reported; they were synthesized in order to attenuate marked fluctuations of L-DOPA (LD) plasma levels and to overcome the problem of low bioavailability of LD. The new compounds were characterized evaluating solubility, chemical stability, apparent partition coefficient (log P) and comparing neostriatum dopamine (DA) levels in freely moving rats after i.p. administration of prodrugs [(+)-4, (+)-5] with prodrugs in liposomal formulations [(+)-4Lip, (+)-5Lip]. All the new compounds showed chemical stability in aqueous buffer solutions (pH 1.3 and 7.4). A relatively slow release of LD in human plasma was observed. Among the studied products, prodrug was able to induce sustained delivery of DA in rat striatal dialysate with respect to equimolar i.p admistration of LD. Furthermore, neostriatum DA concentration after administration of the synthesized prodrugs vs. prodrugs in liposomal formulations was compared (+)-4Lip, (+)-5Lip). The results suggest that cis dimeric prodrug (+)-4 and (+)-4Lip can improve the release of DA in rat brain and demonstrate the potential of these formulations for controlled delivery of antiparkinson agents. SN - 1061-186X UR - https://www.unboundmedicine.com/medline/citation/17090401/Maleic__and_fumaric_diamides_of__OO_diacetyl__L_Dopa_methylester_as_anti_Parkinson_prodrugs_in_liposomal_formulation_ L2 - https://www.tandfonline.com/doi/full/10.1080/10611860600916636 DB - PRIME DP - Unbound Medicine ER -