Administration of Drugs Using Implantable Micropump.

1992 Fiscal Year Final Research Report Summary

• Project/Area Number: 02670714
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Fukushima Medical College
• Principal Investigator: YAMAGUCHI Osamu Fukushima Medical College, Urology, associate Prof., 泌尿器科, 講師 (60006814)
• Co-Investigator(Kenkyū-buntansha): FUKAYA Yasuo Urology, 泌尿器科, 助手 (20192304)
• Project Period (FY): 1990 – 1992
• Keywords: DSD / enkephalin / GABA / bacrofen / intrathecal administration / micropump

Research Abstract

Using spinal rabbits, the contribution of enkephalinergic or GABA-minergic activity to neurogenic dysfuction of lower urinary tract was evaluated. At acute stage of spinal cord transection, enkephalinergic activity dominantly increased at the isolated lumbosacral cord, resulting in a strong supression of bladder activity. In chronic spinal rabbits with detrusor sphincter dyssynergia (DSD), GABA antagonists (picrotoxin and phacrofen) never affected the bladder and sphincter activity. This finding would indicate that DSD is further enhanced with a lack of endogenous GABA.
atment of DSD by the intrathercal administration using an implanted micropump. In animals receiving 1 mug/h baclofen, DSD had been improved for 2 weeks. In 5 mug/h bacrofen infusion group, its improvement was sustained during 8 to 12 weeks. Further increase in bacrofen dose (10 mug/h) prolonged the effective period to 12 or 16 weeks. Thus, an excellent therapeutic effect of intrathecal bacrofen infusion was confirmed in chronic spinal rabbits. However, this study could not be performed in patients with DSD because of ethical problems.
The intrathecal injection of GABA agonists extremely increased bladder capacity and abolished both pathologic bladder contraction and striated urethral sphincter activity in chronic spinal rabbits. Based on this result, baclofen was used for the tre