Effect of tamsulosin, a novel alpha 1-adrenoceptor antagonist, on urethral pressure profile in anaesthetized dogs.
1. The effect of tamsulosin (YM617, (R) (-)-S-[2-[[2-(o-ethoxyphenoxy)ethyl]amino] propyl]-2-methoxybenzenesulfonamide HCl), a potent and selective alpha 1-adrenoceptor antagonist, was examined on urethral pressure profile (UPP) and mean arterial blood pressure (MBP) in pentobarbital anaesthetized male dogs. 2. Selective alpha 1-adrenoceptor antagonists tamsulosin (1-100 micrograms kg-1 i.v.), prazosin (1-100 micrograms kg-1 i.v.) and bunazosin (1-100 micrograms kg-1 i.v.) produced a dose dependent reduction in prostatic pressure in the UPP. Doses required to reduce prostatic pressure in UPP by 30% were 3.6 +/- 0.8 (n = 8), 6.9 +/- 1.5 (n = 8) and 4.6 +/- 0.9 (n = 8) micrograms kg-1 i.v., respectively. At the highest dose, tamsulosin exerted less hypotensive effect than prazosin and bunazosin. 3. The calcium antagonist nicardipine (0.1-10 micrograms kg-1 i.v.) and angiotensin converting enzyme inhibitor captopril (10-1,000 micrograms kg-1 i.v.) reduced MBP in a dose dependent manner, but exerted no effect on prostatic pressure in the UPP. The diuretic trichloromethiazide (1-100 micrograms kg-1 i.v.) exerted no effect on UPP or MBP. Treatment with nicardipine (3 micrograms kg-1 i.v.), captopril (100 micrograms kg-1 i.v.) or trichlormethiazide (100 micrograms kg-1 i.v.) did not affect relaxant effect of tamsulosin on prostatic pressure in UPP, or potentiate its hypotensive effect. 4. These results suggest that the alpha 1-adrenoceptor regulates urethral pressure as well as blood pressure in anaesthetized dogs, and that alpha 1-adrenoceptor antagonists may be useful in the treatment of micturition disorders associated with benign prostatic hyperplasia. In addition, as tamsulosin decreased urethral pressure with less hypotension, and as its effect was not influenced by treatment with hypotensive drugs, it may be a useful drug for the treatment of micturition disorders with few cardiovascular side effects.
Sudoh
K
K
Cardiovascular & Atherosclerosis Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd, Ibaraki, Japan.
Tanaka
H
H
Inagaki
O
O
Asano
M
M
Takenaka
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011312:Pressure; D011467:Prostate / Q000187:drug effects* / Q000502:physiology; D011799:Quinazolines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D000077409:Tamsulosin
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D011799:Quinazolines; D013449:Sulfonamides; D002216:Captopril; C018176:bunazosin; D009529:Nicardipine; D000077409:Tamsulosin; D011224:Prazosin