Stability drug-likeness

When assayed in HEK293 cells transfected with the cloned human, rat and guinea pig TRPVl, (23a) showed similar potencies. Not unexpeetedly, (23a) showed poor metabolic stability and a structure-activity study to optimize potency and drug-like properties was initiated. Modification on the left-handed A -aryl section showed that ... 

Frequently monitor the patient for signs of drug toxicity and seizures until the patient s drug concentrations have stabilized. Drug interactions are likely when patients are on more than one AED therefore, closely evaluate the patient s entire medication profile, and change medications or doses to minimize the interaction, if possible. 

Guidelines agree that when antidepressants must be used, they should be combined with a mood-stabilizing drug to reduce the risk of mood switch to hypomania or mania.17,41 The question of which antidepressant drugs are less likely to cause a mood switch is not resolved. Anecdotal reports suggested bupropion may be less likely to cause this effect, but systematic reviews have not supported this conclusion. Prevailing evidence recommends that tricyclic antidepressants be avoided.41,43... 

The aim of the present example was to investigate whether the assessment of an in silico model of metabolic stability from a training set of several hundred drugs or drug-like compounds in human CYP3A4 cDNA-expressed microsomal preparations, would offer a suitable approach to predict the metabolic stability of external compounds. 

Compounds with acceptable pharmaceutical properties, in addition to acceptable biological activity and safety profile, are considered "drug-like" or developable. Typical acceptable pharmaceutical properties for oral delivery of a drug-like molecule include sufficient aqueous solubility, permeability across biological membranes, satisfactory stability to... 

Robust peptide-derived approaches aim to identify a small drug-like molecule to mimic the peptide interactions. The primary peptide molecule is considered in these approaches as a tool compound to demonstrate that small molecules can compete with a given interaction. A variety of chemical, 3D structural and molecular modeling approaches are used to validate the essential 3D pharmacophore model which in turn is the basis for the design of the mimics. The chemical approaches include in addition to N- and C-terminal truncations a variety of positional scanning methods. Using alanine scans one can identify the key pharmacophore points D-amino-acid or proline scans allow stabilization of (i-turn structures cyclic scans bias the peptide or portions of the peptide in a particular conformation (a-helix, (i-turn and so on) other scans, like N-methyl-amino-acid scans and amide-bond-replacement (depsi-peptides) scans aim to improve the ADME properties." ... 

Applying this procedure to investigation of the metabolic stability of CYP2D6, we were able to find a model to correctly classify metabolically stable and unstable compounds. This model was trained using a set of 129 compounds from the Bio-Print [31] database. Drug-likeness and solubility properties were used as primary filter in order to eliminate unattractive compounds and all those compounds classified as not soluble, which are always classified as metabolically stable. The data-... 

Like other drugs, psychotherapeutic drugs can be classified in different ways. The most common way is by therapeutic use, and the four major categories are antipsychotics, antidepressants, antianxiety agents, and mood-stabilizing drugs. 

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