Document Detail

Effect of alpha 1 adrenoceptor antagonists on prostatic pressure and blood pressure in the anesthetized dog.
MedLine Citation:
PMID:  7913781     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: In the current study we have profiled a range of compounds at alpha 1 adrenoceptor subtypes in vitro and have assessed their effects in vivo using the anesthetized dog in an attempt to elucidate the predominant alpha 1 adrenoceptor subtype mediating contractile responses of the canine prostate. METHODS: The affinity of compounds for alpha 1 adrenoceptor subtypes was determined by displacement of [3H] prazosin binding from stably transfected rat 1 fibroblasts expressing alpha 1A, alpha 1B, and alpha 1C, adrenoceptor subtypes. The potency of these agents was then assessed in vivo using an anesthetized dog model allowing simultaneous measurement of prostatic pressure and blood pressure following intravenous (i.v.) administration of phenylephrine (1 to 128 micrograms/kg). RESULTS: All compounds examined in this study showed high and similar affinity for alpha 1 adrenoceptor subtypes, with the exception of 5-Methyl-urapidil, which was selective for alpha 1C (pKi = 9.3) over alpha 1B (pKi = 7.2) and alpha 1A (pKi = 8.1). Doxazosin, terazosin, alfuzosin, and tamsulosin were potent antagonists of phenylephrine responses and in vivo derived "pseudo pA2" determinations showed that the drugs did not discriminate between prostatic and vascular receptors. 5-Methyl-urapidil was also a potent antagonist of phenylephrine-induced responses but was selective for prostatic pressure ("pseudo pA2" = 8.7) over blood pressure ("pseudo pA2" = 7.2). CONCLUSIONS: Data in the present study suggest a predominant role of the alpha 1C adrenoceptor subtype in the contractile response of the canine prostate to phenylephrine in vivo. This model therefore provides a suitable means of assessing putative prostate-selective antagonists for the treatment of benign prostatic hyperplasia.
B A Kenny; A M Naylor; A J Carter; A M Read; P M Greengrass; M G Wyllie
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Urology     Volume:  44     ISSN:  0090-4295     ISO Abbreviation:  Urology     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-08-19     Completed Date:  1994-08-19     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0366151     Medline TA:  Urology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  52-7     Citation Subset:  IM    
Department of Discovery Biology, Pfizer Central Research, Sandwich, Kent, United Kingdom.
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MeSH Terms
Adrenergic alpha-Antagonists / pharmacology*
Affinity Labels
Anesthesia, Intratracheal
Blood Pressure / drug effects*
Dose-Response Relationship, Drug
Doxazosin / pharmacology
Models, Biological
Phenylephrine / pharmacology
Piperazines / pharmacology
Prazosin / analogs & derivatives,  pharmacology
Prostate / drug effects*,  physiology
Quinazolines / pharmacology
Sulfonamides / pharmacology
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/Affinity Labels; 0/Piperazines; 0/Quinazolines; 0/Sulfonamides; 106133-20-4/tamsulosin; 19216-56-9/Prazosin; 34661-85-3/5-methylurapidil; 59-42-7/Phenylephrine; 63590-64-7/Terazosin; 74191-85-8/Doxazosin; 81403-80-7/alfuzosin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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