Lathers C M, Tumer N, Frame V, Roberts J
Pharmacology. 1987;35(1):35-46. doi: 10.1159/000138293.
CGS 10078B (CGS; 1-[2,3-dihydro-1,4-(2S)-benzodioxin-2-yl]-5-[2,3-dihydro-1,4-(2R)- benzodioxin-2-yl]-3-(1R,5S)-aza-1,5-pentanediol methane sulfonate) is an agent with alpha- and beta-receptor and calcium channel blocking actions. To study its antiarrhythmic activity, cats were anesthetized with alpha-chloralose, ventilated, and given atropine and gallamine. CGS (10 or 20 mg/kg, i.v.) was infused 15 min prior to ouabain. Bolus injections of ouabain (25 micrograms/kg, i.v.) were given every 15 min until death (D). Some cats were pretreated with reserpine (R; 5 mg/kg, i.p.) 24 h prior to the experiment. In other cats 6-hydroxydopamine (6-OHDA; 20 mg/kg, i.v.) was administered 3 days prior to CGS 20 mg/kg and ouabain. Data were compared with those of Lathers [Eur. J. Pharmacol. 64: 95, 1980], i.e., with 12 cats who received only ouabain and with 11 pretreated with timolol (T; 5 mg/kg, i.v.) prior to ouabain. After CGS (10 or 20 mg/kg, i.v.), but just prior to the first dose of ouabain, the blood pressure (BP) was decreased (p less than 0.05) from control (165 +/- 6 vs. 96 +/- 7, and 136 +/- 5 vs. 90 +/- 10 mm Hg, respectively). Comparable heart rate (HR) values were also decreased (p less than 0.05) from 225 +/- 17 to 166 +/- 14 and from 193 +/- 8 to 152 +/- 6 beats/min. 11 min after T, BP and HR had decreased (p less than 0.05) from 133 +/- 6 to 103 +/- 7 mm Hg and from 134 +/- 4 to 104 +/- 6 beats/min, respectively. Ouabain did not influence these decreases in BP and HR. CGS (10 or 20 mg/kg, i.v.) increased (p less than 0.05) the time to ouabain-induced arrhythmia (AR) and D. The magnitude of the protection appeared to be similar to that afforded by T. R given prior to CGS (20 mg/kg, i.v.) also increased the time to ouabain-induced AR and D while 6-OHDA increased the time to AR. The CGS protection against ouabain-induced AR was still present in animals pretreated with R or 6-OHDA. This indicates that the antiarrhythmic affect is not dependent upon adrenergic neuronal blockade.
CGS 10078B（CGS；1-[2,3-二氢-1,4-(2S)-苯并二噁英-2-基]-5-[2,3-二氢-1,4-(2R)-苯并二噁英-2-基]-3-(1R,5S)-氮杂-1,5-戊二醇甲磺酸盐）是一种具有α和β受体阻断及钙通道阻滞作用的药物。为研究其抗心律失常活性，用α-氯醛糖对猫进行麻醉、通气，并给予阿托品和加拉明。在哇巴因给药前15分钟静脉注射CGS（10或20毫克/千克）。每隔15分钟静脉推注一次哇巴因（25微克/千克）直至死亡（D）。一些猫在实验前24小时腹腔注射利血平（R；5毫克/千克）。在其他猫中，在给予20毫克/千克CGS和哇巴因前3天静脉注射6-羟基多巴胺（6-OHDA；20毫克/千克）。将数据与Lathers[《欧洲药理学杂志》64:95,1980]的数据进行比较，即与12只仅接受哇巴因的猫以及11只在哇巴因前静脉注射噻吗洛尔（T；5毫克/千克）的猫的数据进行比较。静脉注射CGS（10或20毫克/千克）后，但在首次给予哇巴因之前，血压（BP）较对照降低（p<0.05）（分别为165±6对96±7，以及136±5对90±10毫米汞柱）。相应的心率（HR）值也降低（p<0.05），从225±17降至166±14次/分钟，以及从193±8降至152±6次/分钟。注射T后11分钟，BP和HR分别从133±6降至103±7毫米汞柱以及从134±4降至104±6次/分钟（p<0.05）。哇巴因并未影响BP和HR的这些降低。静脉注射CGS（10或20毫克/千克）增加（p<0.05）了哇巴因诱导的心律失常（AR）和死亡的时间。保护程度似乎与T所提供的相似。在静脉注射CGS（20毫克/千克）前给予R也增加了哇巴因诱导的AR和死亡的时间，而6-OHDA增加了AR的时间。在预先用R或6-OHDA处理的动物中，CGS对哇巴因诱导的AR的保护作用仍然存在。这表明抗心律失常作用不依赖于肾上腺素能神经阻滞。
