Changes in the human light reflex as a measure of the anticholinergic effects of drugs. A comparison with other measures

Summary Single oral doses of atropine, nortriptyline, procyclidine and lactose dummy were administered double-blind to eight healthy young subjects in a balanced, crossover study. Television pupillometry was used to measure the anticholinergic effects of these drugs on the pupil diameter in darkness and the reflex response to light flashes. The sensitivity of this method was compared with conventional autonomic function tests, viz. salivary secretion, radial pulse, forearm sweat gland activity and distance to visual near point. Visual analogue scales were used to obtain subjective measures of sedative drug effects. The expected inhibition of parasympathetic activity was found in most instances with two exceptions: firstly, that nortriptyline failed to affect the pupil despite causing a tachycardia and secondly, that procyclidine gave a bradycardia. The results are discussed with reference to the possible advantages of television pupillometry over conventional pupil measurement in the detection of anticholinergic drug effects.     

Muscarinic signaling is required for spike-pairing induction of long-term potentiation at rat Schaffer collateral-CA1 synapses

Cholinergic input from the basal forebrain and septum to the hippocampus is well known to be critical in learning and memory. Muscarinic induction of theta-frequency oscillations may synchronize pre- and postsynaptic firing and thereby enhance plasticity in the hippocampus. Previous studies have demonstrated that muscarinic activation facilitates long-term potentiation (LTP) induced with tetanus in vitro. In the present study, we tested the role of muscarinic receptor activity in the induction of LTP beyond effects on spike timing by using a spike-pairing (SP) method at Schaffer collateral-CA1 synapses in rat hippocampal slices. Pairings of pre- and postsynaptic action potentials (APs) have been shown to induce LTP when the presynaptic AP precedes the postsynaptic AP by 5-15 ms, but contribution of muscarinic co-activation has not been ruled out. We demonstrate that the mAChR antagonist atropine abolishes LTP induction by SP. Surprisingly, prolonged exposure to the mAChR agonist carbachol inhibits LTP induction by SP, perhaps because of receptor desensitization. These results demonstrate an essential role of cholinergic signaling in this form of hippocampal plasticity.     

Prophylaxis against prostaglandin-induced gastrointestinal side effects

Prostaglandin F2 alpha was administered intravenous drip in 130 patients with missed, incomplete inevitable and septic abortion, intrauterine death and vesicular mole and for therapeutic termination of midtrimester pregnancies. In 84 patients (control group), no prophylactic antiemetic or antidiarrheal drugs were administered, while in 46 patients (study group), an antiemetic (prochlorperazine) and an antidiarrheal (diphenoxylate hydrochloride with atropine sulfate) drug were administered prophylactically before and during prostaglandin infusion. The incidence in vomiting and diarrhea was statistically much less in the study group (P less than 0.0005 for vomiting and P less than 0.005 for diarrhea). There was no statistically significant difference in the success rate of prostaglandin induction in the two groups.     

阿托品对中国仓鼠V79细胞有丝分裂过程的影响

本研究以毒蕈碱型乙酰胆碱受体抑制剂阿托品在离体情况下作用于中国仓鼠Ｖ７９细胞,通过分析Ｖ７９细胞晚末期和早Ｇ１期细胞核细胞质构型,双核细胞频率,探讨了阿托品对哺乳动物离体细胞正常有丝分裂过程的影响。结果发现,阿托品使Ｖ７９细胞的晚末期一早Ｇ１期细胞核和细胞质分裂构型发生显著变化,以核细胞的阿托品可能通过Ｍ型胆碱受体阻断过程而对哺乳动物有丝分裂真实性产生影响。胆碱受体的功能异常可能为非整倍体发生的诱     

胆囊穴穴位用药预防腹腔牵拉反应的临床观察

为观察胆囊穴Innovar复合阿托品、麻黄碱注射用于预防腹腔手术中内脏牵拉反应的效果。将60例胃癌手术病例随机分为两组。试验组A（n=30）：硬膜外麻醉后行双侧胆囊穴药物注射：对照组B（n=30）：仅单纯常规硬膜外麻醉。观察术中探查脏器时BP、HR变化．以及患者精神安定情况和恶心呕吐反应。结果：A组无明显恶心呕吐,患者安静,手术中HR、SBP、DBP相对平稳。提示胆囊穴行Innovar复合阿托品、麻黄碱注射,可抑制腹腔牵拉反应,减轻患者痛苦,利于术中麻醉管理。     

Differential bronchial and pulmonary vascular responses to vagal stimulation in the pig

The pulmonary and bronchial vascular responses and changes in bronchial tone upon vagal stimulation (240 impulses at 2 Hz or 10 Hz) were studied in anaesthetized pigs paralyzed with pancuronium. The acetylcholine-evoked vasodilatation in the tracheobronchial circulation had the same magnitude when using pancuronium or succinylcholine as skeletal muscle relaxants. Atropine-sensitive bradycardia, hypotension and bronchoconstriction were observed upon vagal stimulation. A vasoconstrictor response in the pulmonary vascular bed and clear-cut vasodilatation in the bronchial circulation supplied by the bronchial artery also occurred upon vagal stimulation. The vagallyevoked increase in pulmonary vascular resistance was markedly reduced after atropine while the bronchial vasodilatation was unchanged. This suggests that the vagallyinduced increase in bronchial blood flow was not secondary to changes in the pulmonary circulation. Furthermore, the pulmonary vasoconstrictor response caused by vagal stimulation under control conditions is probably explained by reflex sympathetic activation due to the fall in systemic blood pressure. These data indicate selective vagal non-cholinergic influence of blood flow in the bronchial vascular bed compared to the pulmonary circulation.     

阿托品、士的宁对电刺激家兔大脑皮层感觉区影响丘脑束旁核神经元伤害性放电的作用

家兔在清醒箭毒化人工呼吸下,采用玻璃微电极细胞外记录束旁核痛抑制单位的放电活动,观察电刺激大脑皮层感觉区对束旁核痛抑制单位伤害性放电的影响,并探讨皮层刺激效应的机理。 23例实验表明,皮层刺激可解除痛抑制单位的伤害性抑制反应,但可为静脉注射阿托品(0.3～0.5mg/kg)或士的宁(0.2mg/kg)所阻断,其中两例痛抑制单位的自发放电,随皮层每一刺激脉冲可出现一阵短暂的遏止,这种遏止反应不为士的宁所阻断。提示:大脑皮层及皮层下中枢的胆碱能系统和甘氨酸可能参与皮层对丘脑束旁核痛抑制单位伤害性抑制反应的下行调节;而在皮层每一刺激遏止一阵痛抑制单位的自发放电活动中,甘氨酸可能不占重要地位。     

Neuropeptide Y in the paraventricular nucleus of the hypothalamus stimulates colonic transit by peripheral cholinergic and central CRF pathways

There is evidence suggesting that neuropeptide Y (NPY) as well as corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus (PVN) are involved in the CNS regulation of gastrointestinal (GI) function. We studied the effects of NPY or Y1-and Y2-receptor agonists microinjected into the PVN on colonic transit. Microinjection of NPY into the PVN at doses of 0.15-1.5 microg decreased the colonic transit time of conscious rats up to 49%. Pretreatment with the peripherally acting cholinergic antagonist atropine methyl nitrate (0.1 mg kg-1 i.p.) blocked the NPY into PVN-induced effect on colonic motor function.The agonist of the Y1-receptor, NPY(Leu31, Pro34), as well as the Y2-receptor agonist, NPY(13-36), dose-dependently decreased colonic transit time when microinjected into the PVN (0.05, 0.15 and 0.5 microg). However, the Y1-receptor agonist was more effective. Intracerebroventricular (ICV) application of the CRF-receptor antagonist, alpha-helical-CRF9-41 (50 microg/rat), blocked the NPY effect in the PVN on colonic motor function. In conclusion, stimulation of colonic transit by NPY acting in the PVN was observed. The PVN is more sensitive to agonists acting on the Y1- than on the Y2-receptor to mediate stimulation of propulsive colonic motility. The effect of NPY in the PVN on colonic motor function depends on central CRF and peripheral cholinergic pathways.     

Cardiovascular effects of microinjections of angiotensin II into the nucleus tractus solitarii

The role of the angiotensin II system within the nucleus tractus solitarii (NTS) in central cardiovascular control was investigated by local microinjections of angiotensin II and the angiotensin II receptor antagonist saralasin. Microinjections of 1 ng angiotensin II into the NTS resulted in a monophasic depressor response (-7.3 +/- 1.7 mm Hg), while higher doses were characterized by a biphasic response, with an initial decrease followed by a subsequent increase in blood pressure (10 ng: -4.7 +/- 1.3/+7.9 +/- 1.1 and 100 ng: -2.4 +/- 1.2/+7.5 +/- 1.2 mm Hg). Heart rate decreased significantly following microinjections of 1 and 10 ng angiotensin II (-27 +/- 5.0 and -15 +/- 5.9 bpm), while with 100 ng angiotensin II there was no significant effect on heart rate. Prior i.v. administration of atropine (1 mg/kg) abolished the bradycardia, but did not significantly affect the blood pressure response. Microinjections of saralasin into the NTS elicited a dose-dependent pressor response (10 ng: 6.0 +/- 1.5 mm Hg; 100 ng: 16.8 +/- 3.4 mm Hg) and tachycardia (10 ng: 5 +/- 3.2 bpm; 100 ng: 17 +/- 4.4 bpm). Our data support the hypothesis that angiotensin II acts on specific receptors within the NTS to modulate peripheral cardiovascular responses. The cardiovascular effects elicited by microinjections of the peptide exhibit complicated dose-response relationships. The effects on heart rate, but not on blood pressure, appear to be mediated by parasympathetic activation.