Pharmacological antagonism of facilitatory but not inhibitory effects of serotonin and norepinephrine on excitability of spinal motoneurons

Serotonin (5HT) and norepinephrine (NE) produced long-lasting facilitation of glutamate-evoked activity of spinal motoneurons when applied iontophoretically with small ejection currents into the ventral horn. The facilitation was usually preceded by a brief period of inhibition at the onset of current application to the monoamine-containing barrels. This inhibition did not outlast the current application. Ejection of hydrogen ions produced only inhibition of glutamate-evoked activity with no subsequent facilitation at current offset. The 5HT antagonists, methysergide and metergoline, blocked the facilitation, but not the inhibition of motoneuron excitability caused by 5HT. Similarly, the alpha-adrenergic antagonists, piperoxane and phentolamine, blocked the facilitatory, but not the inhibitory, effects of NE on excitability of motoneurons. Since the inhibitory effects of 5HT and NE could not be blocked with the antagonists used, and since ejection of hydrogen ions also produced inhibition, non-specific causes for the inhibitory effects of 5HT and NE could not be rejected. However, the facilitatory effects of 5HT and NE on excitability of motoneurons were readily blocked by antagonists and were, therefore, attributed to actions on separate 5HT and NE receptors in the ventral horn.     

α1- AND α2-ADRENOCEPTORS OF THE CIRCULAR MYOMETRIUM FROM THE DIOESTROUS GUINEA-PIG

1. In order to investigate the nature of the alpha-adrenoceptors mediating contraction of circular myometrium from dioestrous guinea-pigs, the effects of several adrenoceptor antagonists upon log concentration curves to noradrenaline and phenylephrine have been examined. 2. In the presence of ICI 118,551 and nisoxetine both phenylephrine and noradrenaline produced concentration-dependent contractures of circular myometrium from virgin dioestrous guinea-pigs. Noradrenaline was the more potent and produced larger maximal contractions. Indomethacin (1 mumol/l) decreased the maximum effects of phenylephrine but not those of noradrenaline. Xylazine produced indomethacin-sensitive contractions which were not dose-related and which never exceeded 40% of those evoked by noradrenaline. Responses to xylazine and to noradrenaline, but not those to phenylephrine, were reduced in a low calcium solution. 3. Prazosin produced competitive antagonism of the effects of phenylephrine upon preparations of circular myometrium from virgin and parous dioestrous animals; pA2 values were both 8.1. Phentolamine also competitively antagonized the effects of phenylephrine (virgin animals, pA2=7.7). 4. Both prazosin and phentolamine antagonized the effects of noradrenaline upon preparations from virgin dioestrous animals, however, Schild plot analysis did not indicate a simple bimolecular interaction between agonist and receptors. In the presence of prazosin the alpha 2-adrenoceptor antagonist idazoxan produced dose-dependent parallel shifts in the positions of the log concentration-response curves to noradrenaline; the pA2 was 7.7. In the presence of idazoxan or of indomethacin prazosin competitively antagonized the effects of noradrenaline; the pA2 values were 8.5 and 8.2 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

杏仁核内注射精氨酸加压素心血管效应机制的研究

本工作采用微量法注射法向大鼠杏仁核内注射精氨酸加压素（Ａｒｇ），记录平均动脉血压（ＢＰ）和心率（ＨＲ）的变化。结果显示：Ａｒｇ可使动脉血压升高，心率增加。静脉注射酚妥拉明预先阻断外周α受体，可以完全消除Ａｒｇ在杏仁核的升压效应，但不影响加快心率的效应。而静脉注射阿托品预先阻断外周ｍ受体，对Ａｒｇ在杏仁核的升压和加快心率的效应无明显影响。提示：Ａｒｇ注入杏仁核可引起血压升高，心率加快，Ａｒｇ在中枢的     

Alterations in nociceptirve threshold and morphine-induced analgesia produced by intrathecally administered amine antagonists

Intrathecal administration of either methysergide or phentolamine produced hyperalgesia. This suggests that tonically active serotonergic and noradrenergic neuronal systems modulate sensitivity to nociceptive stimuli at the level of the spinal cord. Methysergide did not attenuate the analgesia induced by either 2.0 or 7.5 mg/kg morphine (s.c.), while phentolamine attenuated the analgesia induced by 2.0, but not 7.5 mg/kg morphine. These findings suggest that bulbospinal serotonergic neurons are not integral components of the neuronal circuitry which mediates opiate-induced analgesia. Noradrenergic neurons, however, appear to mediate a portion of such analgesia.     

硝普钠对充血性心力衰竭患者血小板聚集功能的影响

目的：探讨硝普钠（ＳＮＰ）对充血性心力衰竭（ＣＨＦ）患者血小板聚集功能的影响，并与酚妥拉明（ＰＨＡ）进行比较。方法：ＣＨＦ患者随机分为ＳＮＰ组（１４例）及ＰＨＡ组（２０例），２组患者分别给予ＳＮＰ５０ｍｇ／２５０ｍｌ，滴速３．０～５．０μｇ·ｋｇ－１／ｍｉｎ及ＰＨＡ２０ｍｇ／２５０ｍｌ，滴速２．５～５．０μｇ·ｋｇ－１／ｍｉｎ。于ＰＨＡ和ＳＮＰ静滴结束前，２组患者同时抽血测定血小板聚集率。聚集诱导剂为二磷酸腺苷（ＡＤＰ）、肾上腺素（ＥＮ）及胶原（Ｃｏｌ）。用药前后血小板聚集率比较采用配对ｔ检验。结果：用药后ＳＮＰ组患者各种诱导剂所致血小板聚集率均显著降低（Ｐ均＜０．００１），ＰＨＡ组用药前后无显著性差异。结论：应用ＳＮＰ对ＣＨＦ患者具有广谱抗血小板作用，而ＰＨＡ则无此作用。ＣＨＦ患者应用扩血管药物纠正心力衰竭时选择ＳＮＰ可能有助于防治血栓栓塞并发症的发生。     

Phentolamine mesylate relaxes rabbit corpus cavernosum by a nonadrenergic, noncholinergic mechanism

The contribution of NO-cGMP dependent pathway to phentolamine mesylate-evoked nonadrenergic, noncholinergic relaxation of rabbit corpus cavernosum was investigated in vitro. Stimulation of nonadrenergic, noncholinergic neurons of the rabbit corpus cavernosum elicited frequency-related relaxation that was significantly attenuated by L-NAME (NO synthase inhibitor) or ODQ (an inhibitor of guanylate cyclase). Moreover, tetrodotoxin, a sodium channel blocker, abolished the electrical field stimulation-induced relaxation of rabbit corpus cavernosum, suggesting that neuronal release of NO mediates relaxation to electrical field stimulation. Phentolamine mesylate (30 and 100 nM) dose-dependently enhanced electrical field stimulation-induced relaxation of the rabbit corpus cavernosum. Prazosin (30 microM) and yohimbine (30 microM) failed to affect phentolamine mesylate-mediated nonadrenergic, noncholinergic rabbit penile smooth muscle relaxation, suggesting that phentolamine relaxes rabbit corpus cavernosum independent of alpha-adrenergic receptor blockade. In contrast, pretreatment of the rabbit cavernosal strips with L-NAME significantly-attenuated electrical field stimulation produced relaxations to phentolamine mesylate, suggesting that phentolamine mesylate relaxes rabbit corpus cavernosum by activating NO synthase. The data suggest that phentolamine mesylate relaxes nonadrenergic noncholinergic neurons of the rabbit corpus cavernosum by activating NO synthase and is independent of alpha-adrenergic receptor blockade.     

Stability and compatibility of doxofylline with phentolamine mesilate in 0.9% sodium chloride or 5% dextrose injection for intravenous infusion

What is know and objective: The use of extemporaneously prepared admixtures of drugs must be supported by documentation of their chemical stability. The objective was to assess the physical compatibility and the chemical stability of doxofylline with phentolamine mesilate in 0·9% sodium chloride or 5% dextrose injection for intravenous infusion. Methods: Total volumes of 20 and 1 mL of doxofylline solution and phentolamine mesilate solution, respectively, were added to 250 mL polyolefin bags containing 5% dextrose injection or 0·9% sodium chloride injection. Bags were stored for 24 h at 20–25 °C. Chemical compatibility was measures with high‐performance liquid chromatography, and physical compatibility was determined visually. Results: The samples were clear and colourless when viewed in normal fluorescent room light. The pH value and particulate content of the admixtures exhibited little change. The retentions of the initial concentration of doxofylline and phentolamine mesilate in the admixtures were within 97–105%. Doxofylline and phentolamine mesilate were stable in 5% dextrose injection or in 0·9% sodium chloride for up to 24 h at 20–25 °C. What is new and conclusion: Doxofylline and phentolamine mesilate mixed in both 5% dextrose injection and 0·9% sodium chloride injection in 250 mL multilayer polyolefin bags at concentrations of 0·74 mg/mL and 36·9 μg/mL, respectively, were stable for up to 24 h at 20–25 °C.     

酚妥拉明与硝酸甘油分别联用垂体后叶素治疗支气管扩张咯血的疗效对比

目的观察并对比酚妥拉明、硝酸甘油分别联合垂体后叶素治疗支气管扩张咯血的临床疗效。方法将90例支气管扩张咯血患者随机分为A组和B组,各45例。在常规镇静、抗感染等对症治疗基础上,A组患者予垂体后叶素联合酚妥拉明治疗方案,B组予垂体后叶素联合硝酸甘油用药方案,均以5d为1个疗程,记录并对比两组患者止血时间、1个疗程内咯血量、临床疗效及药物不良反应等指标。结果A组平均止血时间为（6．2±0．8）d,1个疗程内咯血量为（241．5±32．4）mL,低于B组的（6．8±1．1）d及（265．3±54．5）mL,差别均具有统计学意义（P〈0．05）。A组痊愈率（60．00％）与总有效率（100．00％）高于B组（40．00％和95．56％）。A组药物不良反应发生率（15．56％）高于B组（8．89％）,差异不具有统计学意义（P〉0．05）。结论垂体后叶素联合酚妥拉明治疗支气管扩张咯血方案较之联用硝酸甘油方案起效相对更快,疗效更明显,但要注意酚妥拉明的药物不良反应。     

去甲肾上腺素对吗啡依赖大鼠中枢痛觉的调制

目的研究去甲肾上腺素(NE)和酚妥拉明对吗啡依赖大鼠伏核(NAc)内痛兴奋神经元(PENs)和痛抑制神经元(PINs)生物电活动的影响。方法采用NAc内给药的方法,以电脉冲刺激右侧的坐骨神经作为伤害性刺激,用玻璃微电极记录吗啡依赖大鼠NAc内PENs或PINs的电变化。结果 NAc内微量注入NE(4 g.L-1,0.5μl)可使吗啡依赖大鼠NAc中PEN对伤害性刺激反应的痛诱发放电频率减少,潜伏期延长,但PIN痛诱发放电频率增加,抑制时程(ID)缩短,呈现出NE的镇痛效应。NAc内注入酚妥拉明(4g.L-1,0.5μl)产生相反反应,表明酚妥拉明可阻断内源性NE的作用。结论 NE和α-肾上腺素能受体均参与吗啡依赖大鼠NAc内伤害性信息的调控。NAc是调制吗啡依赖大鼠中枢痛觉的重要核团之一。     

微毛诃子对家兔胸主动脉环的作用及其机制

目的： 研究微毛诃子甲醇提取物和乙醇提取物对家兔离体胸主动脉环的作用并探讨其可能的作用机制。 方法： 采用累积加药法,观察0.01~0.08 g·mL^-1微毛诃子对家兔离体胸主动脉环血管张力的影响;观察乙酰胆碱、酚妥拉明预处理对0.01 g·mL^-1微毛诃子缩血管作用的影响;采用Ca²⁺剥夺和复加法,观察0.01 g·mL^-1微毛诃子对细胞内钙释放和外钙内流动脉收缩作用的影响。 结果： 微毛诃子甲醇提取物浓度依赖性对内皮完整的家兔胸主动脉环收缩幅度低于内皮不完整的收缩幅度（P<0.05）,乙醇提取物对内皮完整的家兔胸主动脉环收缩幅度高于内皮不完整的收缩幅度（P<0.05）,且具有浓度依赖性;0.01 g·mL^-1的微毛诃子的甲醇提取物或乙醇提取物均可使乙酰胆碱（Ach,1×10^-5mol·L^-1）、酚妥拉明（10 mg·L^-1）预舒张的血管条收缩;维拉帕米（1×10^-7 mol·L^-1）预处理可消除0.01 g·mL^-1微毛诃子甲醇提取物的缩血管作用;在无Ca²⁺液中,0.01 g·mL^-1的微毛诃子甲醇提取物对去内皮主动脉环的收缩幅度显著低于有Ca²⁺液中的收缩幅度（P<0.05）。 结论： 微毛诃子甲醇提取物和乙醇提取物对家兔离体胸主动脉均有收缩作用;其缩血管作用可能与M受体及α受体有关;微毛诃子甲醇提取物的收缩作用具有内皮依赖性,可能与其促使血管平滑肌细胞外Ca²⁺内流进入细胞有关。