Different drugs
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Understanding Different Drugs: Structural Similarities, Pharmacophore Combinations, and Bioequivalence
Structural Similarities in Marketed Drugs
Drug Substructures and Fragment-Based Drug Discovery
A comprehensive analysis of marketed drugs reveals that a significant number of drugs share structural similarities. Specifically, 15% of 1386 marketed drugs are found as substructures within other drugs, and 30% contain other drugs as substructure fragments. Smaller drugs often appear in multiple larger drugs, with minor structural changes typically retaining the primary pharmacological effects, while larger changes can lead to different pharmacological outcomes. This insight is crucial for fragment-based drug discovery strategies, enhancing our understanding of the chemical building blocks in marketed drugs1.
Twin and Triplet Drugs in Opioid Research
Symmetrical and Nonsymmetrical Twin Drugs
Twin and triplet drugs, which contain two or three pharmacophore components, respectively, are pivotal in opioid research. Symmetrical twin drugs, with identical pharmacophores, tend to produce more potent and selective effects. In contrast, nonsymmetrical twin drugs, which have different pharmacophores, exhibit dual pharmacological activities. Nonsymmetrical triplet drugs, containing two identical and one different pharmacophore, can simultaneously bind multiple receptor sites, enhancing pharmacological action and dual activity. These drugs are evaluated for their in vivo pharmacological effects, synthesis, and overall pharmacology2.
Bioequivalence and Therapeutic Efficacy of Generic vs. Brand-Name Psychoactive Drugs
Differences in Efficacy and Tolerability
The interchangeability of generic and brand-name psychoactive drugs is based on bioequivalence, which requires identical active ingredients, administration routes, and therapeutic effectiveness. However, studies have shown that bioequivalence does not always equate to therapeutic efficacy. For instance, plasma levels of phenytoin were significantly lower after switching from a brand-name to a generic product. Similar issues were observed with carbamazepine and valproic acid, where generic formulations led to a recurrence of convulsions and seizures. Differences in pharmacokinetic variables have also been reported for diazepam and paroxetine mesylate, favoring brand-name drugs. These findings suggest the need for more rigorous analyses of tolerability and efficacy in both patients and healthy subjects3.
Molecular Frameworks of Known Drugs
Common Drug Shapes and Structural Diversity
An analysis of commercially available drugs reveals that half of the drugs can be described by 32 common molecular frameworks, indicating low structural diversity. When considering atom type, hybridization, and bond order, the diversity increases, with 2506 different frameworks among 5120 compounds. This structural data can guide future drug discovery by highlighting common features and potential new drug shapes4.
Conceptual Structure of Drugs Across Different User Groups
Perceived Similarities and Drug Experience
The conceptual structure of drugs varies significantly across groups with different levels of drug experience. Abstainers tend to categorize drugs based on legality rather than pharmacological properties, while experienced users have more sophisticated and pharmacologically based conceptions. This differentiation suggests that early drug behavior involves developing complex and interrelated drug concepts, which should be considered in designing interventions and information campaigns5.
The New Drug Phenomenon
Emergence of New Psychoactive Substances
The drug market has seen significant changes with the rise of new psychoactive substances, driven by commodification and open market sales. These substances, often not controlled under drug laws, are explored for their psychopharmacological effects and side effects. This phenomenon highlights the need for ongoing research and monitoring to address the challenges posed by these new drugs6.
Simultaneous Administration of Drugs with Different Half-Lives
In-Vitro Simulation Model
In clinical chemotherapy, the simultaneous administration of two drugs with different half-lives is common due to their synergistic potential. An in-vitro model has been developed to simulate the first-order elimination kinetics of such drug combinations, allowing for multiple dose regimens of either bolus injections or continuous infusions. This model aids in understanding the pharmacokinetic interactions between drugs7.
Conclusion
The study of different drugs encompasses various aspects, from structural similarities and pharmacophore combinations to bioequivalence and therapeutic efficacy. Understanding these factors is crucial for drug discovery, development, and effective clinical use. The insights gained from these studies can guide future research and improve therapeutic outcomes.
Sources and full results
Most relevant research papers on this topic
Drugs in other drugs: a new look at drugs as fragments.
A significant portion of marketed drugs are contained within other drugs, offering potential for fragment-based drug discovery strategies and enhancing understanding of marketed drug space from a chemical building-block perspective.
Literature Review
Highly CitedTwin and triplet drugs in opioid research.
Twin and triplet opioid drugs show potential in opioid research due to their unique pharmacological effects and synthesis methods.
The bioequivalence and therapeutic efficacy of generic versus brand-name psychoactive drugs.
The essential-similarity requirement should be extended to include rigorous analyses of tolerability and efficacy in actual patients and healthy subjects, as current bioequivalence studies may not fully compare the two drugs.
Systematic ReviewHighly CitedThe properties of known drugs. 1. Molecular frameworks.
The diversity of shapes in known drugs is extremely low, with only 32 most common frameworks describing half of the compounds studied.
Highly CitedConcepts of drugs: differences in conceptual structure across groups with different levels of drug experience.
More experienced drug users have more sophisticated and interrelated concepts about drugs, including those they have not used.
Observational StudyThe new drug phenomenon.
The rise of new drugs is driven by the commodification of psychoactive substances not controlled by drug laws and their sale on an open market, resulting in a growing market for these substances and a need for effective drug policies to address this issue.
Highly CitedIn-vitro model for simultaneous simulation of the serum kinetics of two drugs with different half-lives.
This in-vitro model allows simultaneous simulation of the serum kinetics of two drugs with different half-lives, enabling testing of synergistic drug combinations in clinical chemotherapy.
Highly CitedWhen two drugs are better than one
Searching for drug combinations that work better together than alone can help identify promising treatments for drug-resistant cancer.
Same Drug, Different Dosing: Differences in Dosing for Drugs Approved in the United States, Europe, and Japan
Differences in approved dosing exist for drugs approved in the United States, Europe, and Japan, with half of the studied drugs having lower dosing in Japan compared to the United States or Europe.
Observational StudyHighly Cited