Biphasic effect of apomorphine, an anti-parkinsonian drug, on bladder function in rats.
The effects of anti-parkinsonian drugs on bladder function have been controversial; namely, some aggravated while others alleviated bladder dysfunction in patients with Parkinson disease. These studies, however, did not consider the dose- and time-dependent effects. Therefore, we investigated these effects of apomorphine, an anti-parkinsonian drug and a nonselective dopamine receptor agonist, on the bladder function using normal conscious rats. Consecutive cycles of micturition were analyzed for 30-min periods before and after (over a 4-h period) s.c. administration of a single dose of 0.01 (low), 0.05 (medium), 0.5 (high) mg/kg of apomorphine or saline to the rats. Apomorphine administration produced various effects in relevant urodynamic parameters, although the monitored parameters remained unchanged in saline-administered rats. During filling, low-dose apomorphine induced initial decreases in voiding frequency (VF; defined as the number of voidings during a 15-min period). However, medium- and high-dose apomorphine dose-dependently induced initial increases in VF, and was followed by decreases in VF. These doses also induced initial increase in threshold pressure. During voiding, low-dose apomorphine induced initial increases in micturition volume (MV), which reflected an increase in bladder capacity (BC). However, medium- and high-dose apomorphine dose-dependently induced initial decreases in MV, and was followed by increases in MV. These doses also dose-dependently induced an initial increase in maximum bladder contraction pressure during the early phase after administration. The present study demonstrated that apomorphine displayed a dose- and time-dependent biphasic effect on the normal bladder filling function. These pharmacodynamic characteristics of apomorphine could be applicable to other anti-parkinsonian drugs such as levodopa and nonselective dopamine receptor agonists, and may account for the previous reported conflicting effects of anti-parkinsonian drugs on bladder dysfunction in patients with Parkinson disease, although it needs to be evaluated in disease status.
Uchiyama
T
T
Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. uchiyama@faculty.chiba-u.jp
Sakakibara
R
R
Yoshiyama
M
M
Yamamoto
T
T
Ito
T
T
Liu
Z
Z
Yamaguchi
C
C
Awa
Y
Y
Yano
H-M
HM
Yanagisawa
M
M
Yamanishi
T
T
Hattori
T
T
Kuwabara
S
S
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001058:Apomorphine / Q000009:adverse effects*; D018491:Dopamine Agonists / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D014554:Urination / Q000187:drug effects; D014556:Urine
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D001058:Apomorphine