Pharmacology, behavioral

The mechanism of action of nootropic agents has been proposed to be their abiUty to faciUtate information acquisition, consoHdation, and retrieval (36). No one particular effect has been observed with any consistency for these agents, thus whereas a considerable amount of diverse preclinical pharmacological behavioral data has been generated using these compounds, the significance of these results in predicting clinical efficacy has not been established (43,44). Reviews on the biochemical and behavioral effects of nootropics are available (45—47). 

The hypothesis that HNO is not involved during NO-release from sydnonimines was confirmed by the study of NO-release from C78-0652 109, the dimethyl derivative of SIN-1A (Scheme 6.19). This product closely resembles SIN-1A in its biological and pharmacological behavior, showing a clear NO-dependent vasodilating effect on guinea pig pulmonary arteries and hypotensive action in anesthetized and conscious dog models [105]. 

Liiddens, H. and Korpi, E.R. (1996) GABAa receptors pharmacology, behavioral roles, and motor disorders. Neuroscientist 1 15-23. 

Lieb, L.M., G. Flynn, and N. Weiner. 1994. Follicular (pilosebaceous unit) deposition and pharmacological behavior of cimetidine as a function of formulation. Pharm Res 11 1419. 

In 1964, in order to compare the pharmacological behavior of both antipodes of thalidomide (1), Casini and Ferappi in Italy examined the preparation of (S)-thalidomide (1) from N-phthaloyl-L-glutamine (12) for the first time [85]. Namely, treatment of N-phthaloyl-L-glutamine (12) with one equivalent of thionyl chloride, pyridine, and then triethylamine in dichloromethane at - 30 °C gave (S)-thalidomide (1), [a]p° - 62° (Scheme 17). Although the reported method was straightforward, it was devoid of many synthetic details. 

It has been shown by several authors that, on intravenous application, in many cases an interaction with the blood substances takes place. Thus, PVNO on intravenous application shows a pharmacological behavior somewhat different from that on subcutaneous application. A partially N-oxidized poly(allyldiethylamine) reacts with heparin with the formation of a complex (68). 

Viala et al. published a method for GC detection of chloroquine and monodes-methylchloroquine in hair of patients who had been treated with chloroquine for several months. The samples were washed with detergent (DET) and then dissolved in hot potassium hydroxide. After the extraction with ether, a thin-layer procedure was used for cleaning up. The quantitation was made by GC with a NP-FID. Chloroquine and its metabolite were identified by GC/MS. The GC detection of chloroquine and with NP-FID detector was reported by Ochsendorf et al. They quantitated the drug in different hair sections and found a correlation to the pharmacological behavior of the substance. Couper et al. described a GC screening with NP-FID for antidepressants and antipsychotic drugs in hair from post-mortem cases. 

DSM-IV presents but one version of borderline disorder (a type of histrionic-dependent borderline). Speaking more broadly in this book, we will refer to borderline disorders as including a host of personality "styles" that share the common core features listed above. In addition, it is helpful to delineate three subgroups of borderlines. These subgroups have been derived both by research methods (cluster and factor analysis) and by a method that psychopharmacologist Donald Klein calls "pharmacological behavioral dissection." This latter approach looks at how different groups of patients respond to psychotropic medications based on their response patterns, subtypes can be identified. 

In this study, as a first step in modeling opiate receptor interactions, we have considered the interaction of an ammonium ion and methyl sulfate or phosphate with the series of compounds shown in Figure 1. These compounds, as N-substitutents in rigid opiates such as 5,9 dimethyl, 2 hydroxy, 6,7 benzomorphans, exhibit a broad spectrum of pharmacological behavior from... 

This map (Fig. 21) displays a completely different picture. Now, the molecules are grouped by their pharmacological behavior instead of their structural scaffold. The COX-2-selective drugs (15, 16, 17, 19, 20) are grouped in the same region of the map. Compounds 14 (meloxicam) and 18 (6-mna) show a sHght selectivity for COX-2 and are located between the regions of selectivity and nonselectivity. 

Considering our familiarity with the pharmacological behavior of different sulfonamides, it is fjntstrating, indeed, to concede defeat no correlation appears to exist between their structural or functional characteristics and their tendency to become antigenic determinants. Table I - which has been compiled and averaged from multiple sources - presents biochemical and metabolic studies of various sulfonamides and notes, for each, the reported incidence of sensitization. We have been unable to find a common denominator. Even so, it is instructive to take a critical look at certain hypotheses which have been advanced. 

Refers to modifications such as PEGylation or hyperglycosylation, which alters pharmacological behavior. 

R22. Rosenthal, 8. M., and White, E. C., Studies in hepatic function. VI. A. The pharmacological behavior of certain phthalein dyes. B. The value of selected phthalein compounds in estimation of hepatic function. J. Pharmacol. Exptl. Therap. 24, 265-288 (1924). 

A key to understanding antisense technol-t ogy is to consider it in a pharmacological context. It is essential to understand the structure, function, and metabolism of the receptors for these drugs. As with any of the class of dmgs, it is essential to consider the effects of antisense oligonucleotides in the context of dose-response curves. It is essential to consider the future in the context of advances in antisense biology and medicinal chemistry that result in improved pharmacological behaviors. 

The development of selective muscarinic agonists, thus, has been a major focus of the pharmaceutical industry for the past decade. Many compounds have been synthesized and tested for muscarinic activity, and a few compounds have been introduced into clinical trials. Although compounds like xanomeline (see Fig. 1) have exhibited some beneficial activity in Alzheimer s patients, unwanted side effects have limited their utility. In an attempt to develop ligands with improved activity and selectivity, we synthesized a series of amidine derivatives, including 5-(3-ethyl -1,2,4- oxadiazol -5-y 1) -1,4,5,6- tetrahydropyrimidine trifluboroacetic acid (CDD-0102), and compared its pharmacological, behavioral and toxicological properties with xanomeline. 

Trendelenburg (150) has reviewed some of the history concerning the isolation and pharmacological behavior of ephedrine, which was isolated by Nagai in 1887 and studied byMiura (151). The last author stated that ephedrine produced a respiratory arrest, decreased pulse rate, induced a cardiac arrest in diastole, and a mydriasis in the frog. With dogs and cats a stimulation of the respiration and pulse, clonic convulsions, and hyperthermia are noted. Airila (152) and Morita (153) observed an intense motor stimulation provoked by ephedrine in the rabbit (20 mg.). 

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