Jäkälä P, Viitamaa T, Sirviö J, Riekkinen P, Salonen J, Haapalinna A, Virtanen R, Riekkinen P
Department of Neurology, University of Kuopio, Finland.
Eur J Pharmacol. 1992 Oct 20;221(2-3):351-7. doi: 10.1016/0014-2999(92)90722-g.
The present study investigates the effects of a subchronic continuous infusion of atipamezole, a potent and selective alpha 2-adrenoceptor antagonist, on neocortical high-voltage spindle (HVS) activity in rats. Six days' subcutaneous infusion of atipamezole (0.125 mg/kg per h) with osmotic minipumps decreased HVS activity significantly. The HVS activity-decreasing effect of atipamezole persisted at the same level throughout the infusion. A single subthreshold dose of an alpha 2-adrenoceptor agonist, guanfacine (0.001 mg/kg i.p.), did not affect HVS activity either before or after the continuous atipamezole treatment. The central alpha 2-adrenoceptor blocking effect of atipamezole (0.1 mg/kg per h s.c.) was confirmed to be at the same level after one, three or seven days' infusion, as assessed by measuring the antagonism of detomidine-induced mydriasis in the rat. The serum concentration of atipamezole (0.1 mg/kg per h s.c.) increased slightly from day 3 (37 +/- 11 ng/ml) to day 7 (45 +/- 4 ng/ml). In conclusion, the results of the study suggest that the suppressant effects of atipamezole on neocortical high-voltage spindle activity are preserved during subchronic continuous treatment. In addition, alpha 2-adrenoceptor blockade, as measured in the rat mydriasis model, persists at the same level during subchronic infusion.
本研究调查了亚慢性持续输注阿替美唑（一种强效且选择性的α2 - 肾上腺素能受体拮抗剂）对大鼠新皮质高压纺锤波（HVS）活动的影响。用渗透微型泵皮下输注阿替美唑（每小时0.125毫克/千克）6天，显著降低了HVS活动。在整个输注过程中，阿替美唑降低HVS活动的作用维持在相同水平。在连续阿替美唑治疗之前或之后，单次阈下剂量的α2 - 肾上腺素能受体激动剂胍法辛（腹腔注射0.001毫克/千克）均未影响HVS活动。通过测量大鼠中右美托咪定诱导的瞳孔散大的拮抗作用评估，阿替美唑（每小时0.1毫克/千克皮下注射）的中枢α2 - 肾上腺素能受体阻断作用在输注1天、3天或7天后被证实处于相同水平。阿替美唑（每小时0.1毫克/千克皮下注射）的血清浓度从第3天（37±11纳克/毫升）到第7天（45±4纳克/毫升）略有增加。总之，研究结果表明，在亚慢性持续治疗期间，阿替美唑对新皮质高压纺锤波活动的抑制作用得以保留。此外，在大鼠瞳孔散大模型中测量的α2 - 肾上腺素能受体阻断作用在亚慢性输注期间维持在相同水平。
