Tags

Type your tag names separated by a space and hit enter

CNS delivery of L-dopa by a new hybrid glutathione-methionine peptidomimetic prodrug.
Amino Acids. 2012 Jan; 42(1):261-9.AA

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder associated primarily with loss of dopamine (DA) neurons in the nigrostriatal system. With the aim of increasing the bioavailability of L: -dopa (LD) after oral administration and of overcoming the pro-oxidant effect associated with LD therapy, we designed a peptidomimetic LD prodrug (1) able to release the active agent by enzyme catalyzed hydrolysis. The physicochemical properties, as well as the chemical and enzymatic stabilities of the new compound, were evaluated in order to check both its stability in aqueous medium and its sensitivity towards enzymatic cleavage, providing the parent LD drug, in rat and human plasma. The radical scavenging activities of prodrug 1 was tested by using both the DPPH-HPLC and the DMSO competition methods. The results indicate that the replacement of cysteine GSH portion by methionine confers resistance to oxidative degradation in gastric fluid. Prodrug 1 demonstrated to induce sustained delivery of DA in rat striatal tissue with respect to equimolar LD dosages. These results are of significance for prospective therapeutic application of prodrug 1 in pathological events associated with free radical damage and decreasing DA concentration in the brain.

Authors+Show Affiliations

Dipartimento di Scienze del Farmaco, Università G. D'Annunzio, Via dei Vestini 31, 66100, Chieti, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

21080012

Citation

Pinnen, Francesco, et al. "CNS Delivery of L-dopa By a New Hybrid Glutathione-methionine Peptidomimetic Prodrug." Amino Acids, vol. 42, no. 1, 2012, pp. 261-9.
Pinnen F, Cacciatore I, Cornacchia C, et al. CNS delivery of L-dopa by a new hybrid glutathione-methionine peptidomimetic prodrug. Amino Acids. 2012;42(1):261-9.
Pinnen, F., Cacciatore, I., Cornacchia, C., Mollica, A., Sozio, P., Cerasa, L. S., Iannitelli, A., Fontana, A., Nasuti, C., & Di Stefano, A. (2012). CNS delivery of L-dopa by a new hybrid glutathione-methionine peptidomimetic prodrug. Amino Acids, 42(1), 261-9. https://doi.org/10.1007/s00726-010-0804-z
Pinnen F, et al. CNS Delivery of L-dopa By a New Hybrid Glutathione-methionine Peptidomimetic Prodrug. Amino Acids. 2012;42(1):261-9. PubMed PMID: 21080012.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CNS delivery of L-dopa by a new hybrid glutathione-methionine peptidomimetic prodrug. AU - Pinnen,Francesco, AU - Cacciatore,Ivana, AU - Cornacchia,Catia, AU - Mollica,Adriano, AU - Sozio,Piera, AU - Cerasa,Laura S, AU - Iannitelli,Antonio, AU - Fontana,Antonella, AU - Nasuti,Cinzia, AU - Di Stefano,Antonio, Y1 - 2010/11/17/ PY - 2010/08/20/received PY - 2010/10/29/accepted PY - 2010/11/17/entrez PY - 2010/11/17/pubmed PY - 2012/4/28/medline SP - 261 EP - 9 JF - Amino acids JO - Amino Acids VL - 42 IS - 1 N2 - Parkinson's disease (PD) is a neurodegenerative disorder associated primarily with loss of dopamine (DA) neurons in the nigrostriatal system. With the aim of increasing the bioavailability of L: -dopa (LD) after oral administration and of overcoming the pro-oxidant effect associated with LD therapy, we designed a peptidomimetic LD prodrug (1) able to release the active agent by enzyme catalyzed hydrolysis. The physicochemical properties, as well as the chemical and enzymatic stabilities of the new compound, were evaluated in order to check both its stability in aqueous medium and its sensitivity towards enzymatic cleavage, providing the parent LD drug, in rat and human plasma. The radical scavenging activities of prodrug 1 was tested by using both the DPPH-HPLC and the DMSO competition methods. The results indicate that the replacement of cysteine GSH portion by methionine confers resistance to oxidative degradation in gastric fluid. Prodrug 1 demonstrated to induce sustained delivery of DA in rat striatal tissue with respect to equimolar LD dosages. These results are of significance for prospective therapeutic application of prodrug 1 in pathological events associated with free radical damage and decreasing DA concentration in the brain. SN - 1438-2199 UR - https://www.unboundmedicine.com/medline/citation/21080012/CNS_delivery_of_L_dopa_by_a_new_hybrid_glutathione_methionine_peptidomimetic_prodrug_ L2 - https://dx.doi.org/10.1007/s00726-010-0804-z DB - PRIME DP - Unbound Medicine ER -