Drug modification

Now the drugs don t work They just make you worse... 

Drug modifications are frequently directed at altering properties that influence the concentration of the compound (i.e., its solubility), the duration of action (which is usually related to its stability in tissue), or the ability of drug 

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Table 5.1 Drug modification of the different aspects of neurotransmitter function in synaptic transmission as illustrated in Fig. 5.5...

Carboxylic acids, being weaker acids, react with la-a with inversion of configuration at the anomeric center to yield /2-0-acyl compounds (1,53). This mild and convenient method for 1 -0-acylation of carbohydrates is also useful for pharmacological drug modification (54) or for the resolution of carboxylic acids (53). 

Taste improvement is quite an important aspect of drug modification, especially in pediatric medicine. The extremely bitter taste of some antibiotics, such as clindamycin (3.36) or chloramphenicol (3.37), can be masked successfully by preparing esters or pamoate salts of these drugs, which are very insoluble and therefore have no taste. 

Hansch, C., The use of substituent constants in drug modification, R Farmaco Edition Science, 23,293-320,1968b. 

Assume that a member of the above family has been found to have some desirable activity. In planning a drug modification study, let us consider the following set of functions for substitution at the seven ring positions of naphthalene. 

What has the very limited experience of the past few years using substituent constants and regression analysis contributed to the problem of drug modification as outlined for derivatives of Figure 1 Possibly the most important fact is that the hydrophobic character of the members of almost any congeneric set of drugs must be considered even in... 

Drug modifications to enhance transport across biological barriers... 

DRUG MODIFICATIONS TO ENHANCE TRANSPORT ACROSS BIOLOGICAL BARRIERS... 

Lettieri J. and Fung, H.L. (1978). Improved pharmacological activity via pro-drug modification comparitive pharmacokinetics of sodium gamma-hydroxybutyrate and gamma-butyrolactone. Res. Commun. Chem. Pathol. Pharmacol. 22 107-118. 

Substantial progress has also been reported with regard to the synthesis and testing of nuclease-resistant ribozyme drugs. Modifications including phosphorothioates and nucleoside analogs have been demonstrated to be incorporable in many sites in hammerhead ribozymes, to increase nuclease resistance and support retained ribozyme activity (59-61). In fact, modified relatively nuclease-resistant ribozymes were reported to decrease the target, stromelysin, mRNA levels in knee joints of rabbits after intra-articular injection (62). Further, the pharmacokinetics of a relatively nuclease-stable hammerhead ribozyme were determined after intravenous (i.v.), subcutaneous (s.c.), or intraperitoneal (i.p.) administration to mice. The ribozyme... 

Hansch C, Hatheway GJ, Quinn FR, Greenberg N. Antitumor l-(X-aryl)-3,3-dialkyltriazenes 2. On the role of correlation analysis in decision making in drug modification. Toxicity quantitative structure-activity relationships of l-(X-phenyl)-3,3-dialkyltriazenes in mice. J Med Chem 1978 21 574-577. 

Grieg, N. H. (1989). Drug Delivery to the Brain by Blood-Brain Barrier Circumvention and Drug Modification. In E. A. Neuwelt (Ed.), Implications of the Blood-Brain Barrier and Its Manipulation. New York Plenum Medical Book Co. 

This text provides a foundation for the rational design of drug delivery systems. The factors that influence rates and patterns of drug movement throughout tissues will be considered drug modifications and delivery systems will be presented in the context of normal patterns of drug movement and clearance. 

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