Computational study of the alpha1-Adrenoceptor subtypes and their ligands
Citation:
Berry Matijssen, 'Computational study of the alpha1-Adrenoceptor subtypes and their ligands', [thesis], Trinity College (Dublin, Ireland). School of Chemistry, 2008, pp 241Download Item:
Abstract:
Adrenoceptors (AR) belong to the G-protein coupled receptor (GPCR) family. These
receptors play an important role in regulating many processes in the body related to the
central nervous system, vascular system and many others. The importance of these
receptors as regulators can be further stressed as they are considered promising drug
targets. Currently 40 % of all marketed drugs are targeted at GPCRs. The adrenoceptors
can be subdivided into nine different classes of which the α1-AR class consists of three
subtypes (α14-AR, α1B-AR and α1D-AR). This α1-AR class plays an important role in the
condition known as benign prostatic hyperplasia (BPH). BPH affects 50% of men over 50
years old and with the aging of the population percentage, this percentage is expected to
rise. BPH is manifested by the enlargem ent of prostate tissue that constrains the urethra
Prostatic smooth muscle contraction occurs mainly via the α1A-AR subtype. The effect of
BPH is manifested through the impaired flow of urine through the urethra when is passes
the prostate. Inhibition of the α1A-AR by using an antagonist has shown to increase the
urine flow and therefore, decrease the physiological aspects of BPH. The class α1D-AR is
located in the neck of the bladder where the urine leaves the bladder and it is believed
that inhibiting this receptor could be beneficial in the treatment of BPH. The α1B-AR does
not play a role related to BPH, but is present in the brain. Therefore, it is believed that
inhibition of this receptor could result in unwanted side-effects. Hence, antagonists which
are selective for the α1A-AR and α1D-AR would be useful for treating BPH with reduced side
effects. In our research we develop models for each of the three α1-AR subtypes which
can be used in determining ligand-specific interaction with each subtype.
Author: Matijssen, Berry
Advisor:
Watson, GraemeQualification name:
Doctor of Philosophy (Ph.D.)Publisher:
Trinity College (Dublin, Ireland). School of ChemistryNote:
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Chemistry, Ph.D., Ph.D. Trinity College DublinMetadata
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