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Results for “Drug Design”

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At least 19 recordsLinked to original sources
PubMed1991

Substance abuse: the designer drugs.

Designer drugs, chemically altered compounds derived from federally controlled substances, have become a major cause of addiction and overdose deaths. These drugs include mescaline analogs, synthetic opioids, arylhexylamines, methaqualone derivatives and crack, a new form of cocaine. Sudden changes in mood, weight loss, depression, disturbed sleep patterns, deteriorating school or work performance, marital problems, and loss of interest in friends and social activities may be signs of drug addiction. Life-threatening complications of acute intoxication, such as hyperthermia, seizures, combative and psychotic behavior, and cardiorespiratory collapse, require prompt diagnosis and supportive intervention.

Clinical Protocols↗
PubMed1992

PLS-based quantitative structure-activity relationship for substituted benzamides of clebopride type. Application of experimental design in drug design.

The advantageous approach of using an experimentally designed training set as the basis for establishing a quantitative structure-activity relationship with good predictive capability is described. The training set was selected from a fractional factorial design scheme based on a principal component description of physico-chemical parameters of aromatic substituents. The derived model successfully predicts the activities of additional substituted benzamides of 6-methoxy-N-(4-piperidyl)salicylamide type. The major influence on activity of the 3-substituent is demonstrated.

Benzamides↗
PubMed1992

Computer-aided drug design: getting the best results.

There are two major stages in the design of drug molecules: lead-molecule development and lead-molecule optimization. Whereas a variety of computational chemistry and molecular modeling (CC/MM) techniques are now routinely and successfully applied to the optimization stage of drug design, the generation of initial lead compounds has proven a more difficult problem for the CC/MM approach. Only recently has the design of lead molecules by this route become a subject of active research. This article looks at the factors which must be considered carefully when incorporating CC/MM methods into different aspects of drug-design strategies.

Computers↗
PubMed1992

[Rejection of physico-chemical indices for pathological matrix in a quantitative drug design].

In a quantitative drug design, correlation of coefficient matrix of physico-chemical indices Xi is often pathological when these indices are highly correlated. The regression equation of biological activity Y about these indices Xi obtained in this case is not stable. In this paper, a method is given to obtain a stable regression equation: giving a critical valne alpha and finding out the indices among which correlation coefficient is not less than alpha. The following are the rules to reject some of them. If Xi and Xj is highly correlated (magnitude of rij greater than or equal to alpha, rij is the correlation coefficient of Xi and Xj), and magnitude of rin greater than magnitude of rjn (rin and rjn are correlation coefficients of Xi and Xj about Y, respectively), than the index Xj is rejected, otherwise, Xi is rejected. Stable equation can be obtained by stepwise regression with the remaining indices.

Drug Design↗
PubMed1992

'Designer drugs'. Recognizing and managing their toxic effects.

"Adam," "Eve," "ecstasy," "China white." Illicit street drugs such as these are called designer drugs because they are designed to elicit certain effects and to bypass legal classification. Unfortunately, use and abuse of such substances can lead to serious medical problems and even death. Drs Sternbach and Varon describe the best-known compounds and discuss clinical characteristics and management of designer drug intoxication.

Amphetamines↗
PubMed1992

Understanding the role of oxyradicals in general and in toxic hepatic damage can help safer drug design.

The existence and importance of free radicals are well established both theoretically and in in vivo experiments. Methods and techniques are now available to demonstrate the formation of free radical metabolites of natural substances and xenobiotics. Theories of the biological effects of free radicals could be unified and used for a better understanding of the complex processes of the organism. Pharmacology can gain profit from this multidisciplinary approach, which helps to design safer drugs. The theories of free radicals and the results of experiments with antioxidants could help to decrease the oxidative stress caused by pharmaceutical chemicals.

Animals↗
PubMed1991

New approaches to drug design and delivery based on drug-membrane interactions.

In this review, the complex physical and chemical interactions of drugs with model and biological membranes under normal and pathological conditions are examined at the molecular level. The results of our own published and unpublished structural studies are discussed and correlated with kinetic binding studies to assess the potential role of nonspecific drug interaction with the membrane bilayer in the overall receptor binding mechanism for membrane-bound receptors in heart and brain.

Algorithms↗
PubMed1991

Pattern recognition methods in rational drug design.

Pattern recognition methods have much to offer the drug designer, particularly as the calculation and collation of data, both biological and physicochemical, becomes easier with the widespread use of computer databases, molecular modeling systems, and property prediction packages. Some of the techniques, however, suffer from difficulties in interpretation and the dangers of chance effects have received little attention. The wider use and understanding of these methods is expected to enhance their utility in drug design. Finally, it should be mentioned here that these methods are becoming applied increasingly in other areas of pharmaceutical research, e.g., the analysis of clinical data, and that new techniques for analysis continue to be developed and applied in this field.

Drug Design↗
PubMedDate not supplied

Designing drugs.

Explore the source record for details and available documents.

Drug Design↗
PubMed1992

Automated site-directed drug design using molecular lattices.

Receptor-based drug design is predicated on the knowledge of the structure of a target receptor and the principles of molecule recognition. The objective is to produce a wide diversity of structures that are sterically and electrostatically complementary to a specified receptor site. Many drug-receptor interactions are controlled by a few key receptor groups. This observation leads to a design approach in which one focuses on chemical fragments that putatively interact with the key receptor groups. There then remains the difficult task of joining the fragments into molecular structures that match the spatial patterns of recognition forces in the receptor site. In this paper, we describe a new modeling program, BUILDER, that combines database searching techniques and structure generation algorithms within an interactive graphics modeling environment (MidasPlus). A novel tool for process communication (delegate) is introduced and examples of its use are given. To demonstrate the functionality of the package and its ability to produce novel structures, we examine the active site of HIV-1 protease.

Algorithms↗
PubMed1991

QSAR in environmental sciences and drug design.

Structure-activity relationships are applied in drug design as well as in environmental sciences. Although both fields of application have much in common, there are also some differences. This paper will focus on the similarities and differences in QSAR applied in drug research and environmental research.

Animals↗
PubMed1992

Structure-based strategies for drug design and discovery.

Most drugs have been discovered in random screens or by exploiting information about macromolecular receptors. One source of this information is in the structures of critical proteins and nucleic acids. The structure-based approach to design couples this information with specialized computer programs to propose novel enzyme inhibitors and other therapeutic agents. Iterated design cycles have produced compounds now in clinical trials. The combination of molecular structure determination and computation is emerging as an important tool for drug development. These ideas will be applied to acquired immunodeficiency syndrome (AIDS) and bacterial drug resistance.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Automated site-directed drug design: the generation of a basic set of fragments to be used for automated structure assembly.

If a method is to be developed to assemble putative ligand structures in site-directed drug design, from molecular graphs generated in the site, then basic building blocks are needed. Structure assembly is a combinatoric process that needs to be optimised if it is to be tractable. What has to be determined is whether small molecular fragments can have transferable properties from one molecule to another. In this paper we determine all possible combinations of 3-, 4- and 5-atom aliphatic fragments from a small set of atoms H, C, N, O, F or Cl. The frequency of occurrence of these candidate fragments is searched for in the Cambridge Structural Database. A similar analysis is performed on charged fragments. A more restricted search is carried out for P and S and aromatic structures. A basic set of fragments can be derived that have a significant frequency in known crystal structures. The transferability of fragment properties is discussed in subsequent papers.

Computer-Aided Design↗
PubMed1991

Stalking the elusive designer drugs: techniques for monitoring new problems in drug abuse.

In the 1980s, the clandestine synthesis, distribution, and use of analogs of controlled substances became popular in the United States. These designer drugs comprise analogs of many different classes of psychoactive drugs and present a spectrum of adverse health effects ranging from mood changes to severe neurologic disease. Although there has been no unified program of surveillance for these drugs, a number of articles describing their presence in North American communities have appeared in a variety of publications. This paper summarizes the evidence of designer drug production and use, and recommends effective surveillance efforts that might be adopted by drug abuse prevention and public health agencies.

Designer Drugs↗
PubMed1991

'Designer drugs'. Treating the damage caused by basement chemists.

Use of "designer drugs" has created a new dilemma for physicians. Generally, it is possible to recognize symptoms and signs of intoxication that fit a specific class of substances, such as amphetamine-like effects for the phenylethylamines and opioid effects for the fentanyl analogues. Designer compounds have crossed these boundaries, and toxicology laboratories cannot readily identify them. For now, physicians must rely on clinical presentation and treat accordingly.

Clinical Protocols↗