Study Of Drug-receptor Interactions Research Articles

Application of a stepwise frontal analysis method in cell membrane chromatography

Bio-affinity chromatography is used in the study of drug-receptor interactions. A stepwise frontal analysis (SFA) method was developed based on frontal analysis (FA). A high expression alpha 1A adrenergic receptor (α1A AR) cell membrane chromatography (CMC) method was then developed and combined with SFA to investigate the affinity of three model α1A AR-binding drugs towards α1A AR. Equilibrium dissociation constant (Kd) values for drug-receptor interactions were determined by FA and SFA; results showed that these methods were highly consistent. The results demonstrate that the CMC/SFA method is a time-saving and less wasteful method than traditional method for the evaluation of drug-receptor binding characteristics, and could be used to study the interactions between drugs and membrane receptors.

Characterization of the Ligand Receptor Encounter Complex and Its Potential for in Silico Kinetics-Based Drug Development.

The study of drug-receptor interactions has largely been framed in terms of the equilibrium thermodynamic binding affinity, an in vitro measure of the stability of the drug-receptor complex that is commonly used as a proxy measure of in vivo biological activity. In response to the growing realization of the importance of binding kinetics to in vivo drug activity we present a computational methodology for the kinetic characterization of drug-receptor interactions in terms of the encounter complex. Using trajectory data from multiple Brownian dynamics simulations of ligand diffusion, we derive the spatial density of the ligand around the receptor and show how it can be quantitatively partitioned into different basins of attraction. Numerical integration of the ligand densities within the basins can be used to estimate the residence time of the ligand within these diffusive binding sites. Simulations of two structurally similar inhibitors of Hsp90 exhibit diffusive binding sites with similar spatial structure but with different ligand residence times. In contrast, a pair of structurally dissimilar inhibitors of MDM2, a peptide and a small molecule, exhibit spatially distinct basins of attraction around the receptor, which in turn reveal differences in ligand orientational order. Thus, our kinetic approach provides microscopic details of drug-receptor dynamics that provide novel insight into the observed differences in the thermodynamic binding affinities for the two inhibitors, such as the differences in the entropic contributions to binding. The characterization of the encounter complex, in terms of the structure, topology, and dynamics of diffusive binding sites, offers a new perspective on ligand-receptor interactions and the potential for greater insight into drug action. The method, which requires no prior knowledge of the bound state, is a first step toward the incorporation of ligand kinetics into in silico drug development protocols.

A NMR reverse diffusion filter for the simplification of spectra of complex mixtures and the study of drug receptor interactions

A reverse diffusion filter NMR experiment (Drev) is proposed for the study of small molecules in binding with macromolecules. The filtering efficiency of Drev to eliminate the signals of the macromolecule is shown to be superior to conventional transverse relaxation filters at least for macromolecules containing a significant fraction of flexible residues. The Drev filter was also a useful complement for ligand-based NMR screening in combination with saturation transfer difference experiments.

Interactions of muscarinic drugs with their receptors in single cells of guinea-pig taenia caecum.

Single cells were prepared from the guinea-pig taenia caecum and used for the study of drug-receptor interactions. The cells showed a graded response to carbachol, the dose response curve being shifted in a parallel fashion by atropine, indicating a competitive antagonism. The pA2-value of atropine was in agreement with that estimated using the intact tissue. [3H]QNB (quinuclidinyl benzilate) combined with the single cells, the Scatchard plot yielding a straight line. The dissociation constant of QNB was similar to values estimated in other membrane preparations. The apparent dissociation constants of cholinergic drugs estimated from inhibition of the specific binding of [3H]QNB (0.20 nM) to the single cells by the cholinergic drugs were also in agreement with the values in other membrane preparations. The results indicate that the single smooth muscle cells are useful for the study of drug-receptor interactions.

Why do people choose to purchase generic antibiotics?

Abstrak Latar Belakang: Penggunaan obat generik pada pengobatan infeksi dapat menghemat biaya pengobatan dan membantu masyarakat untuk memperoleh obat yang baik dengan harga terjangkau. Tujuan penelitian ini untuk mengetahui faktor dominan faktor yang mempengaruhi masyarakat membeli antibiotika generik. Metode: Sampel pada penelitian potong lintang ini terdiri dari pasien yang membeli antibiotika generik dan non generik di dua apotek di Purwokerto (Jawa Tengah). Data yang dikumpulkan memakai kuesioner yang berisi pertanyaan beberapa karakteristik subjek, pertimbangan harga, pengalaman penggunaan antibiotika generik sebelumnya, dan asal informasi pemilihan antibiotika generik/non generik. Wawancara dilakukan pada bulan Maret 2010 pada jam kerja apotek pukul 8 pagi sampai 9 malam WIB terhadap subjek yang baru saja membeli antibiotika generik dan antibiotika non generik. Regresi Cox digunakan untuk mengetahui faktor dominan terhadap pembelian antibiotika generik. Hasil: Di antara 100 responden, 71% subjek membeli antibiotik generik. Subjek yang membeli dan tidak membeli antibiotika baik generik maupun non generik terdistrusi sama dalam hal jenis kelamin, tingkat pendapatan , tingkat pendidikan, dan sumber informasi untuk membeli obat antibiotika generik dan non generik. Pertimbangan harga merupakan faktor dominan untuk membeli obat antibiotik generik. Subjek yang memperimbangkan harga memiliki kemungkinan tiga kali lebih besar untuk membeli antibiotika generik dibandingkan yang tidak memperimbangkan harga [risiko relatif ( RR) = 2.94; 95%CI=1, 64-5, 29). Kesimpulan: Faktor harga menjadi alasan pasien membeli antibiotik generik di Purwokerto. Hal ini merupakan masukan bagi pemerintah untuk menetapkan strategi lain guna meningkatkan penggunaan antibiotik generik. ( Health Science Indones 2010; 1: 33 - 36) Kata kunci: harga, antibiotika, generik, non generik Abstract Background: Generic antibiotics use help community to get economic infectious diseases threat. The study aimed to analyze dominant factors that influence community to purchase generic antibiotics. Methods: Subjects of this cross sectional study were patients who purchased generic and non generic antibiotics in two selected private pharmacies in March 2010. We were collected information on several characteristics of subjects, price consideration, generic antibiotics experiences, and information resource before purchased generic and non generic antibiotics. Data was collected in pharmacy working hours. Cox regression was used to identify dominant risk factors on consideration to purchase generic antibiotics. Results: Most of subjects were females, low to moderate income. Out of 100 subjects who participated in this study, 71% subjects purchased generic antibiotics. Those who bought generic and non generic antibiotics were similarly distributed with respect to gender, income level, education level, and information resource for purchasing generic and non generic antibiotics. Those who used price consideration had almost 3 fold to purchased generic antibiotics compared to who did not use price consideration [crude relative risk (RR) =2.94; 95%CI=1.64-5.29]. Conclusion: Price consideration influences patient’s decision to purchase generic antibiotics. This result can be important information for government to conduct another strategy to increase generic antibiotics use. ( Health Science Indones 2010; 1: 33- 36)

Structural, chemical topological, electrotopological and electronic structure hypotheses.

The first important hypothesis in the prediction of properties of synthesized molecules is the structural hypothesis. In the study of drug-receptor interactions, the case where the three-dimensional structure of the receptor is known allows the application of molecular simulation and energy calculations to estimate the binding affinity for a proposed series of compounds. The chemical topological hypothesis permits the description of molecular structures without using concepts such as force or energy. These notions would not be as dominant as supposed since they should be able to be deduced from topology. Although topological descriptors are able to describe specific physicochemical properties, there is no any mechanistic interpretation for topological descriptors, but they can be considered as essential magnitudes, able to describe molecular structure as an alternative and independent approach, since they allow an algebraic description of the structure itself. The hypothesis is based on the ability of topological descriptors for the prediction of virtually any kind of structure-related macroscopic property, and to design directly new compounds showing predetermined properties. It is possible to design new lead drugs ignoring the explicit mechanism of action, but only by topological similarity with other active compounds. This is a basic difference with all the conventional methods based on the use of physical variables, which need to know the specific drug-receptor interaction. The electrotopological hypothesis may be considered a synthesis of both previous hypotheses. Finally, the electronic structure hypothesis is formulated.

Drugs affecting smooth muscle.

While it is tempting and often desirable to regard smooth muscle as a single entity, different types have anatomical, physiological, and pharmaco­ logical differences. In this review of the recent literature on the effect of drugs on various kinds of mammalian smooth muscle the mechanism of drug action has been emphasized when possible and studies of drug-receptor interactions in smooth muscle have been examined. Page limitations pre­ vented citing many worthy investigations but the papers selected, in our opin­ ion, contained promising findings apt to influence future studies of drugs affecting smooth muscle. Past reviews in this series have emphasized the effects of drugs on electrical activity or the role of various ions in the re­ sponse mechanism. Our approach has been to write a more general review.