Piperidinecarboxamides with potential CNS and cardiovascular properties.
Several 1- and 2-(2-phenylethyl)piperidinecarboxamides were prepared and subjected to preliminary pharmacological studies. Moderate to strong activity by several compounds was observed in modified dopa potentiation tests in mice.
6 Non-Tricyclic Antidepressants
Publisher Summary This chapter discusses recent developments in “non-tricyclic antidepressants” and the test methods on which the conclusion of “probably therapeutically active” is based have been evaluated. The chapter discusses the activities of the various new structures, classified by structural resemblance. Some general structure-activity relations (SAR) are also discussed in the chapter. In general, the therapeutic properties of tricyclic antidepressant drugs are attributed to their inhibition of a transmitter uptake by monoaminergic neurons in the central nervous system. This hypothesis is based mainly on the pharmacological properties of these tricyclics in animal experiments viz. the antagonism of monoamine depleting agents, the potentiation of directly or indirectly acting amine agonists, and the decrease in amine uptake processes by appropriate cells or cell fragments. In the non-tricyclic antidepressant, structures there are promising drugs in which the side effects of the tricyclics are absent.
Rational Design, Synthesis and Evaluation of γ-CD-Containing Cross-Linked Polyvinyl Alcohol Hydrogel as a Prednisone Delivery Platform
This study describes the in-silico rational design, synthesis and evaluation of cross-linked polyvinyl alcohol hydrogels containing γ-cyclodextrin (γ-CDHSAs) as platforms for the sustained release of prednisone (PDN). Through in-silico studies using semi-empirical quantum mechanical calculations, the effectiveness of 20 dicarboxylic acids to generate a specific cross-linked hydrogel capable of supporting different amounts of γ-cyclodextrin (γ-CD) was evaluated. According to the interaction energies calculated with the in-silico studies, the hydrogel made from PVA cross-linked with succinic acids (SA) was shown to be the best candidate for containing γ-CD. Later, molecular dynamics simulation studies were performed in order to evaluate the intermolecular interactions between PDN and three cross-linked hydrogel formulations with different proportions of γ-CD (2.44%, 4.76% and 9.1%). These three cross-linked hydrogels were synthesized and characterized. The loading and the subsequent release of PDN from the hydrogels were investigated. The in-silico and experimental results showed that the interaction between PDN and γ-CDHSA was mainly produced with the γ-CDs linked to the hydrogels. Thus, the unique structures and properties of γ-CDHSA demonstrated an interesting multiphasic profile that could be utilized as a promising drug carrier for controlled, sustained and localized release of PDN.