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Computational study of the alpha1-Adrenoceptor subtypes and their ligands
Matijssen, Berry
THESIS 8602 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 ?1-AR class consists of three subtypes (?14-AR, ?1B-AR and ?1D-AR). This ?1-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 ?1A-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 ?1A-AR by using an antagonist has shown to increase the urine flow and therefore, decrease the physiological aspects of BPH. The class ?1D-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 ?1B-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 ?1A-AR and ?1D-AR would be useful for treating BPH with reduced side effects. In our research we develop models for each of the three ?1-AR subtypes which can be used in determining ligand-specific interaction with each subtype.
Keyword(s): Chemistry, Ph.D.; Ph.D. Trinity College Dublin
Publication Date:
2008
Type: Doctoral thesis
Peer-Reviewed: Unknown
Language(s): English
Institution: Trinity College Dublin
Citation(s): Berry Matijssen, 'Computational study of the alpha1-Adrenoceptor subtypes and their ligands', [thesis], Trinity College (Dublin, Ireland). School of Chemistry, 2008, pp 241
Publisher(s): Trinity College (Dublin, Ireland). School of Chemistry
Supervisor(s): Watson, Graeme
First Indexed: 2019-05-03 06:42:59 Last Updated: 2019-11-29 07:08:47