Vogh B P, Doyle A S
J Pharmacol Exp Ther. 1981 Apr;217(1):51-6.
Single cerebrospinal fluid (CSF) samples, taken 7 min after the i.v. administration of tracer 22Na+, provided data for calculation of rate constants for entry of Na+ into CSF from plasma. Four carbonic anhydrase (CA) inhibitors and certain other drugs were studied in terms of 1) ability to reduce the entry of Na+ into CSF and 2) level of drug in plasma. Dose-response curves were generated for the CA inhibitors. Complete CA inhibition in this system is defined by kin 0.017 to 0.019 min-1, a reduction of about 35% from the control kin for Na+. Acetazolamide, ethoxzolamide and methazolamide were fully inhibitory at 20 mg/kg. Significant decreases, approximately 19%, were caused by 2 mg/kg of acetazolamide or ethoxzolamide; methazolamide unaccountably was less effective at this dose. Benzolamide was relatively inactive, but gave full effect at 150 mg/kg. The diuretics furosemide and bumetanide and the steroid dexamethasone showed no activity against Na+ entry. In considering these responses, attention is given to drug affinity for CA and to properties affecting access of inhibitors to CSF-secreting sites. There is a well recognized correlation between the movement of Na+ from plasma into CSF and the secretion of CSF. These data may, therefore, be taken as indicators of the relative ability of the drugs to decrease CSF flow.
在静脉注射示踪剂22Na+ 7分钟后采集的单个脑脊液（CSF）样本，为计算Na+从血浆进入脑脊液的速率常数提供了数据。研究了四种碳酸酐酶（CA）抑制剂和某些其他药物，涉及以下两个方面：1）降低Na+进入脑脊液的能力；2）血浆中的药物水平。生成了CA抑制剂的剂量-反应曲线。该系统中完全的CA抑制作用定义为kin为0.017至0.019分钟-1，比Na+的对照kin降低约35%。乙酰唑胺、乙氧唑胺和甲醋唑胺在20mg/kg时具有完全抑制作用。2mg/kg的乙酰唑胺或乙氧唑胺可导致显著降低，约为19%；甲醋唑胺在此剂量下效果不佳，原因不明。苯磺酰胺相对无活性，但在150mg/kg时产生完全作用。利尿剂呋塞米和布美他尼以及类固醇地塞米松对Na+进入无活性。在考虑这些反应时，关注药物对CA的亲和力以及影响抑制剂进入脑脊液分泌部位的特性。Na+从血浆进入脑脊液的运动与脑脊液的分泌之间存在公认的相关性。因此，这些数据可作为药物降低脑脊液流量相对能力的指标。
