[The distribution and localization of alpha 1-adrenoceptor agonist on the bladder and urethra of female rats].
The distribution of selective alpha 1-adrenoceptor agonist 1-(2',5'-dimethoxyphenyl)-2-glycinamidoethanol hydrochloride, midodrine, and its active metabolite 1-(2',5'-dimethoxyphenyl)-2-aminoethanol, DMAE, was evaluated on bladder and urethra of 8-weeks and 52-weeks old female rats. Prior to the intravenous injection of 14C-labeled midodrine and DMAE, bilateral ureters were ligated to prevent drug uptake from the urinary tract. In 8-weeks rats, 14C-midodrine activity was significantly (p less than 0.01) higher in the bladder than in the femoral muscle, which served as a control for drug distribution. Similarly, higher uptake of 14C-DMAE was observed in the bladder than in the femoral muscle (p less than 0.01) and the urethra (p less than 0.05). In 52-weeks rats, there was no significant difference of midodrine uptake among these tissues. However, significantly higher uptake of 14C-DMAE was observed in the urethra than in the femoral muscle (p less than 0.05). Compared with midodrine, the concentration of DMAE was significantly increased in the bladder of 8-weeks rat and in the urethra of 52-weeks rats (respectively, p less than 0.05). In autoradiogram, the grains corresponding to midodrine and DMAE were diffusely distributed on the smooth muscles of bladder (mainly bladder neck and trigone) and urethra. The grains were also recognized on the vessels and perivascular areas of these tissues. These findings support that midodrine and DMAE could be effective for stress incontinence, because these drugs are known to bind specifically to alpha 1-adrenoceptor.
Moriyama
N
N
Department of Urology, Branch Hospital, Faculty of Medicine, University of Tokyo.
Tajima
A
A
Takahashi
S
S
Homma
Y
Y
Higashihara
E
E
Aso
Y
Y
Minagawa
T
T
Ota
K
K
Okuyama
S
S
D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics*; D000818:Animals; D005260:Female; D008879:Midodrine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014521:Urethra / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; C006146:ST 1059; D008879:Midodrine