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Receptor Pharmacology (receptor + pharmacology)

Distribution by Scientific Domains
Medical Sciences80%

Selected Abstracts

Development of ultra short-acting muscle relaxant agents: History, research strategies, and challenges

MEDICINAL RESEARCH REVIEWS, Issue 6 2005
Laszlo Gyermek
Author has reviewed the literature and his own work related to the chemistry, pharmacology, and clinical aspects of new muscle relaxants. Emphasis has been placed on the basic science concepts and technologies (e.g. structure,activity relationships, nicotinic receptor pharmacology, and investigation of side effects) behind the development of rapidly and short acting nondepolarizing muscle relaxants. © 2005 Wiley Periodicals, Inc. [source]

Translating 5-HT4 receptor pharmacology

NEUROGASTROENTEROLOGY & MOTILITY, Issue 12 2009
G. J. Sanger
Abstract, Since metoclopramide was first described (in 1964) there have been several attempts to develop compounds which retained gastrointestinal prokinetic activity (via 5-HT4 receptor activation) but without the limiting side effects associated with dopamine D2 receptor antagonism. Early compounds (mosapride, cisapride, renzapride, tegaserod) were identified before several of the 5-HT receptors were even described (including 5-HT4 and 5-HT2B), whereas prucalopride came later. Several compounds were hampered by non-selectivity, introducing cardiac liability (cisapride: activity at human Ether-a-go-go Related Gene) or potentially, a reduced intestinal prokinetic activity caused by activity at a second 5-HT receptor (renzapride: antagonism at the 5-HT3 receptor; tegaserod: antagonism at the 5-HT2B receptor). Poor intrinsic activity at gastrointestinal 5-HT4 receptors has also been an issue (mosapride, tegaserod). Perhaps prucalopride has now achieved the profile of good selectivity of action and high intrinsic activity at intestinal 5-HT4 receptors, without clinically-meaningful actions on 5-HT4 receptors in the heart. The progress of this compound for treatment of chronic constipation, as well as competitor molecules such as ATI-7505 and TD-5108, will now be followed with interest as each attempts to differentiate themselves from each other. Perhaps at last, 5-HT4 receptor agonists are being given the chance to show what they can do. [source]

The ,1L -adrenoceptor is an alternative phenotype of the ,1A -adrenoceptor

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2008
C P Nelson
Despite over two decades of research, the molecular identity of the ,1L -adrenoceptor phenotype has remained elusive. In this issue of the BJP, Gray et al. (2008) provide persuasive evidence that the in vivo ,1L -adrenoceptor phenotype requires the expression of the ,1A -adrenoceptor gene. They have shown that in mice lacking the functional ,1A -adrenoceptor gene, ,1L -mediated responses to noradrenaline in prostate smooth muscle are substantially attenuated. These findings support earlier evidence that the ,1L -adrenoceptor profile represents a functional phenotype of the ,1A -adrenoceptor gene product, but additional cell background-dependent factors must act in concert with the ,1A -adrenoceptor protein to determine whether an ,1L - or a classical ,1A -adrenoceptor profile is expressed. The challenge remains to establish the nature of these cellular factors and the mechanism(s) by which they influence G-protein-coupled receptor pharmacology. British Journal of Pharmacology (2008) 155, 1,3; doi:fn1; published online 23 June 2008 [source]

WHAT MAKES A CGRP2 RECEPTOR?

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2007
DL Hay
SUMMARY 1Heterogeneity in the receptors for the neuropeptide calcitonin gene-related peptide (CGRP) has been apparent for nearly 20 years. This is most clearly manifested in the observation of CGRP8,37 -sensitive and -insensitive populations of CGRP-activated receptors. The pA2 values for CGRP8,37 in excess of 7 are widely considered to be the result of antagonism of CGRP1 receptors, whereas those below 7 are believed to be the consequence of antagonism of a second population of receptors, namely CGRP2 receptors. 2However, a multitude of pA2 values exist for CGRP8,37, spanning several log units, and as such no obvious clusters of values are apparent. Understanding the molecular nature of the receptors that underlie this phenomenon is likely to aid the development of selective pharmacological tools to progress our understanding of the physiology of CGRP and related peptides. Because there is active development of CGRP agonists and antagonists as therapeutics, such information would also further this pursuit. 3The CGRP1 receptor is pharmacologically and molecularly well defined as a heterodimer of the calcitonin receptor-like receptor (CL) and receptor activity modifying protein (RAMP) 1. The CL/RAMP1 complex is highly sensitive to CGRP8,37. Conversely, the constituents of the CGRP2 receptor have not been identified. In fact, there is little evidence for a distinct molecular entity that represents the CGRP2 receptor. 4Recent pharmacological characterization of receptors related to CGRP1 has revealed that some of these receptors may explain CGRP2 receptor pharmacology. Specifically, AMY1(a) (calcitonin receptor/RAMP1) and AM2 (CL/RAMP3) receptors can be activated by CGRP but are relatively insensitive to CGRP8,37. 5This, along with other supporting data, suggests that the ,CGRP2 receptor' that has been extensively reported in the literature may, in fact, be an amalgamation of contributions from a variety of CGRP-activated receptors. The use of appropriate combinations of agonists and antagonists, along with receptor expression studies, could allow such receptors to be separated. [source]

GABAC RECEPTOR ION CHANNELS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2004
M Chebib
SUMMARY 1.,The present review gives an overview of studies conducted on GABAC receptors over the past 10 years since the author started at the University of Sydney. It concentrates on the structure,activity relationship profiles of the receptor and how these studies were used to: (i) develop selective GABAC receptor ligands; and (ii) understand the impact of amino acid changes on GABAC receptor pharmacology and function. 2.,Structure,activity relationship studies involving variations of both ligands and their receptor targets are vital to the discovery of drugs that interact selectively with particular native and mutant receptor subtypes. Such agents may be useful for treating anxiety, depression, epilepsyand memory related disorders, such as Alzheimer's disease. [source]