Morikawa K, Hashimoto S, Yamauchi T, Kato H, Ito Y, Gomi Y
Central Research Laboratories, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
Eur J Pharmacol. 1992 Mar 31;213(3):409-15. doi: 10.1016/0014-2999(92)90630-m.
We examined the effects of inaperisone hydrochloride (inaperisone), a new centrally acting muscle relaxant, on bladder function in anesthetized rats and isolated rat tissues. We also investigated its mechanism of action. When a balloon inserted into the bladder was expanded, rhythmic bladder contractions were observed; inaperisone (4 mg/kg i.v.) abolished these contractions, in both normal and decerebrated rats. The bladder tonus or bladder contraction induced by peripheral stimulation of the pelvic nerve was barely inhibited by inaperisone (4 mg/kg i.v.), but this dose of inaperisone abolished the efferent discharge from the pelvic nerve that accompanied the rhythmic bladder contractions. The doses of intracerebroventricularly (i.c.v.) and intrathecally injected inaperisone which abolished the rhythmic bladder contractions were 10 and 100 micrograms, respectively. The inhibitory effects of inaperisone (4 mg/kg i.v.) were not diminished by naloxone (1 mg/kg i.v.) or by bicuculline (0.5 mg/kg i.v.), but were diminished by phaclofen (30 mg/kg i.v. or 300 micrograms i.c.v.). The specific binding of [3H]baclofen to rat brain synaptosomal membranes was barely inhibited by inaperisone (up to 1 mM). From these results, it is speculated that, among other possible mechanisms, inaperisone inhibits the micturition reflex by acting indirectly on GABAB receptors in the brainstem.
我们研究了新型中枢性肌肉松弛剂盐酸伊哌立松（伊哌立松）对麻醉大鼠和离体大鼠组织膀胱功能的影响。我们还研究了其作用机制。当插入膀胱的球囊扩张时，可观察到膀胱有节律的收缩；伊哌立松（静脉注射4mg/kg）可消除正常大鼠和去大脑大鼠的这些收缩。伊哌立松（静脉注射4mg/kg）对盆腔神经外周刺激诱导的膀胱张力或膀胱收缩几乎没有抑制作用，但该剂量的伊哌立松可消除伴随膀胱节律性收缩的盆腔神经传出放电。脑室内（i.c.v.）和鞘内注射伊哌立松消除膀胱节律性收缩的剂量分别为10和100微克。伊哌立松（静脉注射4mg/kg）的抑制作用不会因纳洛酮（静脉注射1mg/kg）或荷包牡丹碱（静脉注射0.5mg/kg）而减弱，但会因巴氯芬（静脉注射30mg/kg或脑室内注射300微克）而减弱。伊哌立松（高达1mM）对[3H]巴氯芬与大鼠脑突触体膜的特异性结合几乎没有抑制作用。从这些结果推测，在其他可能的机制中，伊哌立松通过间接作用于脑干中的GABAB受体来抑制排尿反射。
