ascorbic-acid has been researched along with nipecotic-acid* in 2 studies
2 other study(ies) available for ascorbic-acid and nipecotic-acid
| Article | Year |
|---|---|
Transporter-mediated effects of diclofenamic acid and its ascorbyl pro-drug in the in vivo neurotropic activity of ascorbyl nipecotic acid conjugate.
Continuing our studies on SVCT2 ascorbic acid (AA) transporter-mediated drug delivery of neurotropic agents, we have now investigated the in vitro intracellular uptake of Diclofenac (Diclo) and its conjugate (AA-Diclo), both characterized by high affinity for the SVCT2 transporter. We have also investigated the in vivo uptake mechanism of AA-conjugate of Nipecotic acid (AA-Nipec) and the implication of the transporter-mediated effects of Diclo and AA-Diclo. Diclo resulted as a noncompetitive inhibitor of AA transport, but also showed a sodium-dependent and ascorbate-independent uptake, thus implying the possible involvement of specific transporters in the delivery to the brain of Diclo. This result opens a perspective in the discovery of new strategies in the targeting of this drug to the brain. Inhibitory effects of Diclo and AA-Diclo on the SVCT2 transporter were used to study anticonvulsant effects of AA-Nipec, confirming our hypothesis of an SVCT2-mediated transport in its neurotropic activity. AA-Diclo stability has been also investigated: it is hydrolyzed following a first-order kinetics in buffer, plasma (t(1/2) at about 10 h) and whole blood (t(1/2) at about 3 h), suggesting AA-Diclo as a potential candidate to enhance the short half-life of Diclo in vivo. Topics: Animals; Ascorbic Acid; Brain; Cell Line; Diclofenac; Humans; Male; Mice; Nipecotic Acids; Organic Anion Transporters, Sodium-Dependent; Prodrugs; Seizures; Sodium-Coupled Vitamin C Transporters; Symporters | 2004 |
Design, synthesis and activity of ascorbic acid prodrugs of nipecotic, kynurenic and diclophenamic acids, liable to increase neurotropic activity.
To improve the entry of certain drugs into brain, ascorbic acid (AA) conjugates of these drugs were synthesized and their capacity to interact with SVCT2 ascorbate transporters was explored. Kinetic studies clearly indicate that all of the conjugates were able to competitively inhibit ascorbate transport in human retinal pigment epithelial cells (HRPE). In vivo studies, in a mouse model system, demonstrate that conjugate 3 is better absorbed compared to the nonconjugated parent drug. Topics: Animals; Ascorbic Acid; Biological Transport; Cell Line; Central Nervous System Agents; Diclofenac; Humans; Kinetics; Kynurenic Acid; Mice; Nipecotic Acids; Organic Anion Transporters, Sodium-Dependent; Prodrugs; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Seizures; Sodium-Coupled Vitamin C Transporters; Structure-Activity Relationship; Symporters | 2002 |