Tough times for medicinal chemists: are we to blame?

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...

Antidotes are medicinal substances used to counteract the harmful effects of toxins or drugs in the body. They function in various ways, each uniquely designed to combat specific toxic compounds.
Specific antidotes operate by inhibiting the enzymes that control biochemical pathways, reducing the production of harmful metabolites.
An example of an antidote is atropine, which counteracts the detrimental effects of cholinesterase inhibitors. It achieves this by deactivating muscarinic receptors,...

Drugs, encompassing various chemical compounds from natural sources, lab synthesis, or genetic engineering, elicit different biological responses in living organisms. Some of these responses are desirable or therapeutic, while others are undesirable. The primary goal of administering a drug is to achieve a therapeutic effect, that is, to address a specific disease or health condition. Any concurrent effects outside of this therapeutic outcome are considered undesirable. These undesirable...

The empirical approach to drug therapy optimization relies on correlating pharmacological response with administered dosage. Such an approach can be costly, time-consuming, and often yields poor correlation due to variables like formulation factors and drug elimination characteristics. A more precise approach correlates response with plasma drug concentration or the amount of drug in the body, rather than dosage. This is achieved through pharmacokinetic-pharmacodynamic (PK/PD) modeling, which...

Pharmaceutical poisoning can occur through various channels, impacting an estimated 2 million hospitalized patients in the U.S. annually with serious adverse drug responses. These scenarios encompass both therapeutic uses, such as drug toxicity, where even standard dosages can lead to severe central nervous system depression, and non-therapeutic exposures, including accidental ingestion by children, and environmental and occupational exposures.Unintentional poisonings often involve exploratory...

Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...