Carnitine Conjugate of Nipecotic acid: A new example of dual prodrug

Molecules

Volumn 14, Issue 9, 2009, Pages 3268-3274

  Napolitano, Carmela ^a,c   Scaglianti, Martina ^a,d   Scalambra, Emanuela ^a   Manfredini, Stefano ^a,b   Ferraro, Luca ^a   Beggiato, Sarah ^a   Vertuani, Silvia ^a,b  

^a UNIVERSITY OF FERRARA   (Italy)

^b Ambrosialab Srl   (Italy)

^c Specchiasol Srl   (Italy)

^d NATIONAL UNIVERSITY OF IRELAND   (Ireland)

Author keywords

Increased brain delivery; L carnitine; Molecular conjugation; Nipecotic acid; Prodrug

Indexed keywords

CARNITINE; NIPECOTIC ACID; NIPECOTIC ACID DERIVATIVE; PRODRUG;

ANIMAL; ARTICLE; BRAIN; CHEMISTRY; DOSE RESPONSE; DRUG EFFECT; INTRAPERITONEAL DRUG ADMINISTRATION; METABOLISM; MOUSE; SEIZURE;

ANIMALS; BRAIN; CARNITINE; DOSE-RESPONSE RELATIONSHIP, DRUG; INJECTIONS, INTRAPERITONEAL; MICE; NIPECOTIC ACIDS; PRODRUGS; SEIZURES;

EID: 70349558226     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules14093268     Document Type: Article

References (12)

1. 1.Hansch, C.; Bjorkroth, J.P.; Leo, A. Hydrophobicity and central nervous system agents: On the principle of minimal hydrophobicity in drug design. J. Pharm. Sci. 1987, 76, 663-687.
2. Testa, B.; Carrupt, P.A.; Gaillard, P.; Billois, F.; Weber, P. Lipophilicity in molecular modelling. Pharm. Res. 1996, 13, 335-343.
3. Tamai, I.; Tsuji, A. Transporter mediated permeation of drugs across the blood-brain barrier. J. Pharm. Sci. 2000, 89, 1371-1388.
4. Manfredini, S.; Pavan, B.; Vertuani, S.; Scaglianti, M.; Compagnone, D.; Biondi, C.; Scatturin, A.; Tanganelli, S.; Ferraro, L.; Prasad, P.; Dalpiaz, A. Design, synthesis and activity of ascorbic acid prodrugs of nipecotic, kynurenic and diclophenamic acids, liable to increase neurotropic activity. J. Med. Chem. 2002, 45, 559-562.
5. Bahl, J.J.; Bressler, R. The pharmacology of carnitine. Ann. Rev. Pharmacol. Toxicol. 1987, 27, 257-277.
6. Brass, E.P. L-Carnitine and Its Role in Medicine: From Function to Therapy; Ferrari, R., DiMauro, S., Sherwood, G., Eds.; Academic Press Limited: London, UK, 1992; pp. 21-36.
7. Virmani, M.A.; Rossi, S.; Conti, R.; Spadoni, A.; Arrigoni,- Martelli, E.; Calvani, M. Structural, metabolic and ionic requirements for the uptake of L-carnitine by primary rat cortical cells.Pharm. Res. 1996, 33, 19-27.
8. Dalpiaz, A.; Pavan, B.; Vertuani, S.; Vitali, F.; Scaglianti, M.; Bortolotti, F.; Biondi, C.; Scatturin, A.; Tanganelli, S.; Ferraro, L.; Marzola, G.; Prasad, P.; Manfredini S. Ascorbic and 6-Br-ascorbic acid conjugates as a tool to increase the therapeutic effects of potentially central active drugs. Eur. J. Pharm. Sci. 2005, 24, 259-269.
9. Frey, H. H.; Popp, C.; Loscher, W. Influence of inhibitors of the high affinity GABA uptake on seizure tresholds in mice. Neuropharmacology 1979, 18, 581-590.
10. Yu, Z.; Iryo, Y.; Matsuoka, M.; Igisu, H.; Ikeda M. Suppression of pentylenetetrazol-induced seizures by carnitine in mice. Naunyn Schmiedebergs Arch. Pharmacol. 1997, 355, 545-549.
11. Kim, Y.C.; Zhao, L.X.; Kim, T.H.; Je, S.M.; Kim, E.K.; Choi, H.; Chae, W.G.; Park, M.; Choi, J.; Jahng, Y.; Lee, E.S. Design and synthesis of anticonvulsive agents γ-vinyl GABA-based potential dual acting prodrugs and their biological activities. Bioorg. Med. Chem. Lett. 2000, 10, 609-614.
12. Nassereddine-Sebaei, M.; Crider, A.M.; Carrol, R.T.; Hinko, C.N. Determination of m-nitrophenol and nipecotic acid in mouse tissues by high-performance liquid chromatography after administration of anticonvulsant m-nirophenyl-3-piperidinecarboxylate hydrochloride. J. Pharmaceut. Sci. 1993, 82, 39-43.