In vivo experiments for the evaluation of alpha 1-adrenoceptor antagonistic effects of SGB-1534 on canine urethra.
The alpha 1-adrenoceptor blocking effects of SGB-1534 on the urethral smooth muscle were compared in in vivo lower urinary tract preparations of anesthetized dogs, with the effects of other alpha 1-adrenoceptor antagonists, prazosin and bunazosin. Hypogastric nerve stimulation and selective administration of phenylephrine to the urethra and bladder through the cannulated right external iliac artery (i.a.) elicited reproducible frequency- and dose-dependent increases in intra-urethral pressure. Intra-bladder pressure was increased by the nerve stimulation but not by i.a. phenylephrine. SGB-1534, prazosin or bunazosin (0.1-10 micrograms/kg i.v.) dose dependently suppressed the urethral contraction evoked by the nerve stimulation and i.a. phenylephrine but did not influence the bladder contraction elicited by nerve stimulation. The alpha 1-adrenoceptor blocking potency of SGB-1534 was approximately 2.3 and 8.1 times greater than that of prazosin and bunazosin, respectively. The results indicate that alpha 1-adrenoceptors may mediate mainly the urethral contraction induced by hypogastric nerve stimulation and i.a. phenylephrine, and that SGB-1534 was more potent alpha 1-adrenoceptor blocking activity than prazosin and bunazosin in the canine urethra.
Imagawa
J
J
Department of Pharmacology, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Akima
M
M
Sakai
K
K
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007001:Hypogastric Plexus / Q000187:drug effects; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D014521:Urethra / Q000187:drug effects* / Q000294:innervation
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D010656:Phenylephrine; C042712:SGB 1534; C018176:bunazosin; D011224:Prazosin