Showing papers on "Atropine published in 2016"

Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning

Abstract: The cardioprotection afforded by remote ischaemic conditioning (RIC) is mediated via a complex mechanism involving sensory afferent nerves, the vagus nerve, and release of a humoral blood-borne factor. However, it is unknown whether release of the protective factor depends on vagal activation or occurs independently. This study aimed to evaluate the co-dependence of the neural and humoral pathways of RIC, focussing on the vagus nerve and intrinsic cardiac ganglia. In the first study, anesthetised rats received bilateral cervical vagotomy or sham-surgery immediately prior to RIC (4 × 5 min limb ischemia-reperfusion) or sham-RIC. Venous blood plasma was dialysed across a 12-14 kDa membrane and dialysate perfused through a naive-isolated rat heart prior to 35-min left anterior descending ischemia and 60-min reperfusion. In the second study, anesthetised rats received RIC (4 × 5-min limb ischemia-reperfusion) or control (sham-RIC). Dialysate was prepared and perfused through a naive-isolated rat heart in the presence of the ganglionic blocker hexamethonium or muscarinic antagonist atropine, prior to ischemia-reperfusion as above. Dialysate collected from RIC-treated rats reduced infarct size in naive rat hearts from 40.7 ± 6.3 to 23.7 ± 3.1 %, p < 0.05. Following bilateral cervical vagotomy, the protection of RIC dialysate was abrogated (42.2 ± 3.2 %, p < 0.05 vs RIC dialysate). In the second study, the administration of 50-μM hexamethonium (45.8 ± 2.5 %) or 100-nM atropine (36.5 ± 3.4 %) abrogated the dialysate-mediated protection. Release of a protective factor following RIC is dependent on prior activation of the vagus nerve. In addition, this factor appears to induce cardioprotection via recruitment of intrinsic cardiac ganglia.

Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review

Abstract: Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as "cholinergic crisis" (i.e. diarrhea, sweating, salivation, miosis, bronchoconstriction). Exposure to high doses of sarin can result in tremors, seizures, and hypothermia. More seriously, build-up of ACh at neuromuscular junctions also can cause paralysis and ultimately peripherally-mediated respiratory arrest which can lead to death via respiratory failure. In addition to its primary action on the cholinergic system, sarin possesses other indirect effects. These involve the activation of several neurotransmitters including gamma-amino-butyric acid (GABA) and the alteration of other signaling systems such as ion channels, cell adhesion molecules, and inflammatory regulators. Sarin exposure is associated with symptoms of organophosphate-induced delayed neurotoxicity (OPIDN) and organophosphate-induced chronic neurotoxicity (OPICN). Moreover, sarin has been involved in toxic and immunotoxic effects as well as organophosphate-induced endocrine disruption (OPIED). The standard treatment for sarin-like nerve agent exposure is post-exposure injection of atropine, a muscarinic receptor antagonist, accompanied by an oxime, an AChE reactivator, and diazepam.

Characterization of cardiovascular reflexes evoked by airway stimulation with allylisothiocyanate, capsaicin, and ATP in Sprague-Dawley rats

Abstract: Acute inhalation of airborne pollutants alters cardiovascular function and evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the effect of capsaicin [transient receptor potential (TRP) vanilloid 1 (TRPV1) agonist], AITC [TRP ankyrin 1 (TRPA1) agonist], and ATP (P2X2/3 agonist) on bronchopulmonary sensory activity and cardiovascular responses of conscious Sprague-Dawley (SD) rats. Single fiber recordings show that allyl isothiocyanate (AITC) and capsaicin selectively activate C fibers, whereas subpopulations of both A and C fibers are activated by stimulation of P2X2/3 receptors. Inhalation of the agonists by conscious rats caused significant bradycardia, atrioventricular (AV) block, and prolonged PR intervals, although ATP-induced responses were lesser than those evoked by AITC or capsaicin. Responses to AITC were inhibited by the TRP channel blocker ruthenium red and the muscarinic antagonist atropine. AITC inhalation also caused a biphasic blood pressure response: a brief hypertensive phase followed by a hypotensive phase. Atropine accentuated the hypertensive phase, while preventing the hypotension. AITC-evoked bradycardia was not abolished by terazosin, the α1-adrenoceptor inhibitor, which prevented the hypertensive response. Anesthetics had profound effects on AITC-evoked bradycardia and AV block, which was abolished by urethane, ketamine, and isoflurane. Nevertheless, AITC inhalation caused bradycardia and AV block in paralyzed and ventilated rats following precollicular decerebration. In conclusion, we provide evidence that activation of ion channels expressed on nociceptive airway sensory nerves causes significant cardiovascular effects in conscious SD rats via reflex modulation of the autonomic nervous system.

Autonomic modification of intestinal smooth muscle contractility.

Abstract: Intestinal smooth muscle contracts rhythmically in the absence of nerve and hormonal stimulation because of the activity of pacemaker cells between and within the muscle layers. This means that the autonomic nervous system modifies rather than initiates intestinal contractions. The practical described here gives students an opportunity to observe this spontaneous activity and its modification by agents associated with parasympathetic and sympathetic nerve activity. A section of the rabbit small intestine is suspended in an organ bath, and the use of a pressure transducer and data-acquisition software allows the measurement of tension generated by the smooth muscle of intestinal walls. The application of the parasympathetic neurotransmitter ACh at varying concentrations allows students to observe an increase in intestinal smooth muscle tone with increasing concentrations of this muscarinic receptor agonist. Construction of a concentration-effect curve allows students to calculate an EC50 value for ACh and consider some basic concepts surrounding receptor occupancy and activation. Application of the hormone epinephrine to the precontracted intestine allows students to observe the inhibitory effects associated with sympathetic nerve activation. Introduction of the drug atropine to the preparation before a maximal concentration of ACh is applied allows students to observe the inhibitory effect of a competitive antagonist on the physiological response to a receptor agonist. The final experiment involves the observation of the depolarizing effect of K(+) on smooth muscle. Students are also invited to consider why the drugs atropine, codeine, loperamide, and botulinum toxin have medicinal uses in the management of gastrointestinal problems.

Protection against ventricular fibrillation via cholinergic receptor stimulation and the generation of nitric oxide.

Abstract: Implantable cardiac vagal nerve stimulators are a promising treatment for ventricular arrhythmia in patients with heart failure. Animal studies suggest the antifibrillatory effect may be nitric oxide (NO) dependent, although the exact site of action is controversial. We investigated whether a stable analogue of acetylcholine could raise ventricular fibrillation threshold (VFT), and whether this was dependent on NO generation and/or muscarinic/nicotinic receptor stimulation.VFT was determined in Langendorff perfused rat hearts by burst pacing until sustained VF was induced. Carbamylcholine (CCh, 200 nmol/L, n = 9) significantly (P < 0.05) reduced heart rate from 292 ± 8 to 224 ± 6 bpm. Independent of this heart rate change, CCh caused a significant increase in VFT (control 1.5 ± 0.3, CCh 2.4 ± 0.4, wash 1.1 ± 0.2 mA) and flattened the restitution curve (n = 6,) derived from optically mapped action potentials. The effect of CCh on VFT was abolished by a muscarinic (atropine, 0.1μmol l(-1) , n = 6) or a nicotinic receptor antagonist (mecamylamine, 10 μmol l(-1) , n = 6). CCh significantly increased NOx content in coronary effluent (n = 8), but not in the presence of mecamylamine (n = 8). The nNOS inhibitor AAAN (10 μmol l(-1) , n = 6) or soluble guanylate cyclase (sGC) inhibitor ODQ (10 μmol l(-1) , n = 6) prevented the rise in VFT with CCh. The NO donor sodium nitrprusside (SNP 10μmol/L, n = 8) mimicked the action of CCh on VFT, an effect that was also blocked by atropine (n = 10).These data demonstrate a protective effect of CCh on VFT that depends upon both muscarinic and nicotinic receptor stimulation, where the generation of NO is likely to be via a neuronal nNOS/sGC dependent pathway. This article is protected by copyright. All rights reserved.

Tramadol state-dependent memory: involvement of dorsal hippocampal muscarinic acetylcholine receptors.

Abstract: The effects on tramadol state-dependent memory of bilateral intradorsal hippocampal (intra-CA1) injections of physostigmine, an acetylcholinesterase inhibitor, and atropine, a muscarinic acetylcholine receptor antagonist, were examined in adult male NMRI mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention. Post-training intra-CA1 administration of an atypical μ-opioid receptor agonist, tramadol (0.5 and 1 μg/mouse), dose dependently impaired memory retention. Pretest injection of tramadol (0.5 and 1 μg/mouse, intra-CA1) induced state-dependent retrieval of the memory acquired under the influence of post-training tramadol (1 μg/mouse, intra-CA1). A pretest intra-CA1 injection of physostigmine (1 μg/mouse) reversed the memory impairment induced by post-training administration of tramadol (1 μg/mouse, intra-CA1). Moreover, pretest administration of physostigmine (0.5 and 1 μg/mouse, intra-CA1) with an ineffective dose of tramadol (0.25 μg/mouse, intra-CA1) also significantly restored retrieval. Pretest administration of physostigmine (0.25, 0.5, and 1 μg/mouse, intra-CA1) by itself did not affect memory retention. A pretest intra-CA1 injection of the atropine (1 and 2 μg/mouse) 5 min before the administration of tramadol (1 μg/mouse, intra-CA1) dose dependently inhibited tramadol state-dependent memory. Pretest administration of atropine (0.5, 1, and 2 μg/mouse, intra-CA1) by itself did not affect memory retention. It can be concluded that dorsal hippocampal muscarinic acetylcholine receptor mechanisms play an important role in the modulation of tramadol state-dependent memory.

Evaluation of the benefit of the bispyridinium compound MB327 for the antidotal treatment of nerve agent-poisoned mice.

Abstract: The potency of the bispyridinium non-oxime compound MB327 [1,1'-(propane-1,3-diyl)bis(4-tert-butylpyridinium) diiodide] to increase the therapeutic efficacy of the standard antidotal treatment (atropine in combination with an oxime) of acute poisoning with organophosphorus nerve agents was studied in vivo. The therapeutic efficacy of atropine alone - or atropine in combination with an oxime, MB327, or both an oxime and MB237 - was evaluated by the determination of LD50 values of several nerve agents (tabun, sarin and soman) in mice with and without treatment. The addition of MB327 increased the therapeutic efficacy of atropine alone, and atropine in combination with an oxime, against all three nerve agents, although differences in the LD50 values only reached statistical significance for sarin. In conclusion, the addition of the compound MB327 to the standard antidotal treatment of acute poisonings with nerve agents was beneficial regardless of the chemical structure of the nerve agent, although at the dose employed, MB327 in combination with atropine, or atropine and an oxime, provided only a modest increase in protection ratio. These results from mice, and previous ones from guinea-pigs, provide consistent evidence for additional, albeit modest, efficacy resulting from the inclusion of the antinicotinic compound MB327 in standard antidotal therapy. Given the typically steep probit slope for the dose-lethality relationship for nerve agents, such modest increases in protection ratio could provide significant survival benefit.

Comparison of the treatment effects of methoxamine and combining methoxamine with atropine infusion to maintain blood pressure during spinal anesthesia for cesarean delivery: a double blind randomized trial.

Abstract: Objective Hypotension is a common complication of spinal anesthesia for cesarean delivery. Atropine is a vagus nerve blocker that can antagonize vagus excitation to mitigate the reflex bradycardia. We aimed to assess the effect of methoxamine-atropine therapy in treating spinal anesthesia hypotension for cesarean section. Patients and methods This is a double-blind randomized controlled study. Women under spinal anesthesia for elective caesarean delivery received boluses of methoxamine 2 mg alone (Group M, n = 40), or with addition of atropine 0.1 mg (Group MA1, n = 40), atropine 0.2 mg (Group MA2, n = 40) or atropine 0.3 mg (Group MA3, n = 40) upon a maternal systolic pressure ≤ 80% of baseline. The primary endpoint was systolic blood pressure and the secondary endpoints were maternal heart rates, instant neonatal heart rates, umbilical artery pH and umbilical artery base excess. Results Changes in systolic blood pressure were similar among the four groups. The incidences of bradycardia in groups M and MA1 were significantly higher than those in group MA2 and MA3. The fetal heart rates after delivery in groups MA2 and MA3 were higher than those in group M and MA1 but within the normal range. The acid-base status had no difference in the four groups. Conclusions Methoxamine-atropine combination has a similar efficacy to methoxamine alone but has an increased hemodynamic stability and a less adverse effect occurrence.

Possible Mechanisms for Functional Antagonistic Effect of Ferula assafoetida on Muscarinic Receptors in Tracheal Smooth Muscle.

Abstract: BACKGROUND The contribution of histamine (H1) receptors inhibitory and/or β-adrenoceptors stimulatory mechanisms in the relaxant property of Ferula assa-foetida. (F. asafoetida) was examined in the present study. METHODS We evaluated the effect of three concentrations of F. asafoetida extract (2.5, 5, and 10 mg/mL), a muscarinic receptors antagonist, and saline on methacholine concentration-response curve in tracheal smooth muscles incubated with β-adrenergic and histamine (H1) (group 1), and only β-adrenergic (group 2) receptors antagonists. RESULTS EC50 values in the presence of atropine, extract (5 and 10 mg/mL) and maximum responses to methacholine due to the 10 mg/mL extract in both groups and 5 mg/mL extract in group 1 were higher than saline (P < 0.0001, P = 0.0477, and P = 0.0008 in group 1 and P < 0.0001, P = 0.0438, and P = 0.0107 in group 2 for atropine, 5 and 10 mg/mL extract, respectively). Values of concentration ratio minus one (CR-1), in the presence of extracts were lower than atropine in both groups (P = 0.0339 for high extract concentration in group 1 and P < 0.0001 for other extract concentrations in both groups). CONCLUSION Histamine (H1) receptor blockade affects muscarinic receptors inhibitory property of F. asafoetida in tracheal smooth muscle.

Developmental nicotine exposure alters cholinergic control of respiratory frequency in neonatal rats

Abstract: Prenatal nicotine exposure with continued exposure through breast milk over the first week of life (developmental nicotine exposure, DNE) alters the development of brainstem circuits that control breathing. Here, we test the hypothesis that DNE alters the respiratory motor response to endogenous and exogenous acetylcholine (ACh) in neonatal rats. We used the brainstem-spinal cord preparation in the split-bath configuration, and applied drugs to the brainstem compartment while measuring the burst frequency and amplitude of the fourth cervical ventral nerve roots (C4VR), which contain the axons of phrenic motoneurons. We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh. The main findings include: (1) atropine reduced frequency similarly in controls and DNE animals, while curare caused modest slowing in controls but no consistent change in DNE animals; (2) DNE greatly attenuated the increase in C4VR frequency mediated by exogenous ACh; (3) stimulation of nAChRs with ACh in the presence of atropine increased frequency markedly in controls, but not DNE animals; (4) stimulation of mAChRs with ACh in the presence of curare caused a modest increase in frequency, with no treatment group differences. DNE blunts the response of the respiratory central pattern generator to exogenous ACh, consistent with reduced availability of functionally competent nAChRs; DNE did not alter the muscarinic control of respiratory motor output. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1138-1149, 2016.

Cardiovascular Effects of the Essential Oil of Croton argyrophylloides in Normotensive Rats: Role of the Autonomic Nervous System

Abstract: Cardiovascular effects of the essential oil of Croton argyrophylloides Muell. Arg. (EOCA) were investigated in normotensive rats. In saline-pretreated anesthetized or conscious rats, intravenous (i.v.) injection of the EOCA induced dose-dependent hypotension. Dose-dependent tachycardia was observed only in conscious rats. In anesthetized rats, cervical bivagotomy failed to enhance EOCA-induced hypotension but unmasked significant bradycardia. In conscious rats, i.v. pretreatment with methylatropine, but not with atenolol or L-NAME, reduced both hypotensive and tachycardiac responses to EOCA. However, hexamethonium pretreatment reverted the EOCA-induced tachycardia into significant bradycardia without affecting the hypotension. In aortic ring preparations precontracted with phenylephrine, EOCA induced a concentration-dependent relaxation that was significantly reduced by vascular endothelium removal and pretreatment with atropine, indomethacin, or glibenclamide but remained unaffected by pretreatment with L-NAME or TEA. It is concluded that i.v. treatment with EOAC decreased blood pressure probably through an active vascular relaxation rather than withdrawal of sympathetic tone. Muscarinic receptor stimulation, liberation of the endothelium-derived prostacyclin, and opening KATP channels are partially involved in the aortic relaxation induced by EOCA and in turn in the mediation of EOCA-induced hypotension. EOCA-induced tachycardia in conscious rats appears to be mediated reflexly through inhibition of vagal drive to the heart.

Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber).

Abstract: The present study investigated the cholinergic system in the African naked mole-rat (Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M1 and M4. The protein sequences for the subtypes m 1-5 of the naked mole-rat were compared to that of the house mouse (Mus musculus) using basic local alignment search tool (BLAST). The presence and function of M1 and M4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies with [(3)H]-N-methylscopolamine. The BLAST test revealed 95 % protein sequence homology showing the naked mole-rat to have the genetic potential to express all five muscarinic acetylcholine receptor subtypes. A significant reduction in pain behavior was demonstrated after administration of 8.4 mg/kg in the formalin test. Administration of 50 mg/kg VU0152100 resulted in a non-significant tendency towards antinociception. The antinociceptive effects were reversed by the muscarinic acetylcholine receptor antagonist atropine. Binding studies indicated presence of muscarinic acetylcholine receptors with a radioligand affinity comparable to that reported in mice. In conclusion, muscarinic acetylcholine receptor subtypes are present in the naked mole-rat and contribute to antinociception in the naked mole-rat.

Investigating and comparing effects of atropine and physostigmine in peripheral pain examination due to formalin injection on rats

Abstract: There areseveral neurotransmittersat feel the pain and processing nervoussystem, and until now cholinergic system has not been well studied in this field. The purpose of this research is investigating effects of atropine and physostigmine on the response of formalin pain test. We divided 50 male wistar head rats into 5 groups , first group ( saline normal injection 5 μ ) , second group ( 1% formalin injection into 50 μ ) , third group ( physostigmine injection 0/1 mg / kg ) , fourth group (atropine injection 2 mg / kg ) , fifth group ( atropine injection 2 mg / kg and physostigmine 0/1 mg/kg ) , after formalin injection , the animals were placed inside mirror pain machine and it was recorded pain response at the time ranges 0-5 and 15-45 . Results investigated with spss software and ANOVA and Duncan’s test. Formalin injection causes pain response in both time ranges. Atropine injection alone had no effect on pain response. Physostigmine effect alone, with a significant reduction (p< 0/05) in the number of foot motions in both stage and duration causesof licking and biting in the 15-45 minutes stage . Atropine and physostigmine injections in fifth group cause significant reduction in the number of foot motions and duration of licking and biting in the time range of 15-45 minutes.Perhaps there is a close relationship between cholinergic system and peripheral pain that can be taken through the action of muscarinic receptors.

Central anticholinergic syndrome vs. idiosyncratic reaction triggered by a small IV dose of atropine.

Abstract: A 58-year-old male was scheduled to undergo radical gastrectomy for cancer under general anesthesia. The patient developed agitation and irregular breathing after receiving a single dose of atropine (0.5 mg) to treat bradycardia immediately prior to induction of anesthesia. Within 5 min after the atropine injection, the patient became unresponsive with facial flushing and diaphoresis. When a drop in oxygen saturation was observed, a laryngeal mask airway was inserted after administering a small bolus dose of propofol (80 mg) and the patient was ventilated with 100% oxygen. Physostigmine was not administered because of the relatively low dose of atropine and the fact that his symptoms were not totally consistent with central anticholinergic syndrome (CAS). The differential diagnosis at the time also included an acute cardiovascular event and an idiosyncratic reaction to atropine. The patient fully recovered within 80 min from this highly unusual reaction to a single 0.5 mg IV dose of atropine.

Effects of cholinergic system in antinociception induced by H1 and H2 receptor antagonists on somatic pain in Rats

Abstract: The present study was aimed to investigate the peripheral effects of chlorpheniramine and ranitidine and their relationship with cholinergic system on the somatic pain in rats. The somatic pain was induced by using formalin test. The effects of H1 and H2 receptor antagonists, chlorpheniramine and ranitidine, respectively, on formalininduced pain was studied in rats. Physostigmine and atropine were subcutaneously injected alone and also in combination with chlorpheniramine and ranitidine. Formalin 1% produced biphasic pain response. Chlorpheniramine and ranitidine significantly reduced the second phase of pain (p<0.05). Physostigmine at doses 0.4mg/kg significantly reduced the second phase of pain. Atropine (2 mg/kg) had no significant effect in the first and second phases. Pre-treatment of chlorpheniramine (20mg/kg) before physostigmine (0.4mg/kg) prevented physostigmine induced antinociception. Ranitidine (40mg/kg) before physostigmine (0.4mg/kg) significantly suppressed the antinociceptive effects of physostigmine. Atropine before chlorpheniramine and ranitidine reversed the analgesic effects of chlorpheniramine and ranitidine. These results indicate that physostigmine has been able to inhibit the somatic pain through the cholinergic muscarinic receptors. Both of the histamine H1 and H2 receptor antagonists have analgesic effects and histamine H2 but not H1 antagonist probably is involved in the analgesic effects induced by physostigmine.

Symptoms of Central Anticholinergic Syndrome After Glycopyrrolate Administration in a 5-Year-Old Child.

Abstract: Anesthesia-related central anticholinergic syndrome (CAS) is most commonly associated with administration of atropine or scopolamine, whereas glycopyrrolate is an extremely rare cause of CAS. Here, we report a case of CAS in a 5-year-old boy admitted to the intensive care unit. Immediately after the administration of glycopyrrolate, he became agitated and developed apnea, hypertension, tachycardia, and anuria. Although the present case describes a rare cause of CAS, it is an important reminder of an iatrogenic condition that is presumably underdiagnosed in the operating theater as well as the intensive care unit.

The Effect of Muscarinic Receptor Modulators on the Antinociception Induced by CB2 Receptor Agonist, JWH133 in Mice.

Abstract: There is no published study regarding the interaction between muscarinic receptor modulators and antinociception induced by cannabinoid receptor (CB2) agonist. The effect of pilocarpine (a muscarinic agonist) and atropine (a muscarinic antagonist) on JWH-133 (a CB2 agonist) induced analgesia in mice was studied. First the analgesic effect of JWH-133 (0.001-1 mg/Kg) or pilocarpine (2.5-20 mg/kg) or atropine (0.2-5 mg/kg) was evaluated. Subsequently, the effect of co-administration of pilocarpine (2.5 mg/kg) or atropine (5 mg/kg) and JWH-133 (0.001-1 mg/Kg) were studied too. JWH-133 and pilocarpine provoked antinociception in mice but atropine did not. Pilocarpine potentiated the analgesic effect of JWH-133 but atropine antagonized that. It can be concluded that JWH-133 induced antinociception is affected by muscarinic receptor modulators in mice.

Structure activity relationship of Atropine analogues with muscarinic acetyl choline M1 receptor: A molecular docking based approach

Abstract: Anticholinergics are used in the treatment of a variety of conditions. Some of the important conditions are: chronic obstructive pulmonary disease (COPD),asthma, motion sickness, dizziness, toxicity by organophosphorus insecticides or compounds like muscarine, conditions inducing high blood pressure and symptoms due to Parkinsonism. Atropine, falling under anticholinergic class of drug consists of l- as well as d- forms of hyoscyamine.The action of which is solely due to its levo form. Atropine counteracts the actions of acetylcholine and other esters of choline, thus is also termed as antimuscarinic agent. Due to the immense use of atropine, it was thought to design novel atropine congeners and to compare their binding affinities with the standard drug Tiotropium for binding at the active site of acetyl choline esterase. The results showed that none of the analogues processed dock scores comparable to Tiotropium. But the study gave us insight about the binding modes of anticholinergics. So, in future studies, more effective analogues will be designed and will be taken for in vitro studies.

Acute Pulmonary Edema following Panic Attack in a Patient without Evidence of Heart Disease

Abstract: A 35-year-old woman was admitted because of organophosphate pesticide self-poisoning. At the time of admission in the emergency department of clinical toxicology, she was agitated. Evaluation of vital signs revealed a pulse rate of 148/min, systolic/diastolic blood pressure of 109/88 mm Hg, and respiratory rate of 20/min. She was afebrile and had plenty of oral secretions. Her pupils were mydriatic and reactive to light. Examination of the chest showed bilateral rales. Other organs revealed no pathologic sign or symptoms on physical examination. Computed tomography scan of the brain was normal. Serum cholinesterase level was 5%, and red-cell acetylcholinesterase activity was 0.3. She had no premorbid illness. After the injection of 4 mg of atropine, all muscarinic signs disappeared. This was followed by the infusion of atropine at a rate of 0.5 mg/h; the dose was titrated as per her clinical response and signs of atropinization. Over the next 2 days, she did not need further atropine. On day 4 after admission (i.e., after she had not need any atropine infusion or other treatments for organophosphate poisoning for 2 days), she suddenly developed hypertension crisis with systolic/diastolic blood pressure of 230/150 mmHg, cold sweating, tachycardia, and tachypnea. Chest examination revealed basilar wet rales. Chest X-ray presented diffuse bilateral alveolar infiltration. ECG was normal. Considering the clinical diagnosis of acute cardiogenic pulmonary edema, we started an intravenous infusion of nitroglycerin and furosemide and an intravenous injection of morphine. Twelve hours later, blood pressure was controlled and the rales disappeared. Bedside echocardiography showed normal left ventricular systolic and diastolic functions and normal right ventricular size and function. There was no significant valvular heart disease. Psychiatric consultation confirmed anxiety disorder and panic attack. Treatment with fluoxetine and clonazepam was commenced. During the course of her hospital stay and after her hospital discharge, outpatient follow-up showed no hypertension crisis. We conclude that panic attack and its hypertensive crisis may be severe enough to develop pulmonary edema even in young healthy adults with no comorbidity and with structurally normal heart. (Iranian Heart Journal 2016; 17(1): 71-73)

Neonatal capsaicin administration impairs postnatal development of the cardiac chronotropy and inotropy in rats.

Abstract: The present study evaluated the impact of neonatal administration of capsaicin (neurotoxin from red hot pepper used for sensory denervation) on postnatal development of the heart rate and ventricular contractility. In the rats subjected to capsaicin administration (100 mg/kg) on postnatal days 2 and 3 and their vehicle-treated controls at the ages of 10 to 90 days, function of the sympathetic innervation of the developing heart was characterized by evaluation of chronotropic responses to metipranolol and atropine, norepinephrine concentrations in the heart, and norepinephrine release from the heart atria. Sensory denervation was verified by determination of calcitonin gene-related peptide levels in the heart. Direct cytotoxic effects of capsaicin were assessed on cultured neonatal cardiomyocytes. Capsaicin-treated rats displayed higher resting heart rates, lower atropine effect, but no difference in the effect of metipranolol. Norepinephrine tissue levels and release did not differ from controls. Contraction force of the right ventricular papillary muscle was lower till the age of 60 days. Significantly reduced viability of neonatal cardiomyocytes was demonstrated at capsaicin concentration 100 micromol/l. Our study suggests that neonatal capsaicin treatment leads to impaired maturation of the developing cardiomyocytes. This effect cannot be attributed exclusively to sensory denervation of the rat heart since capsaicin acts also directly on the cardiac cells.

Atropine is more efficient than ZM241385 to reduce a drastic level of fade caused by cisatracurium at 50 Hz

Abstract: The effects of atropine (non selective muscarinic antagonist) and ZM241385 (A 2A receptors antagonist) in the cisatracurium-induced drastic (100%) level of fade at 50 Hz (10 s) (100% Fade) were compared in the phrenic nerve-diaphragm muscle preparations of rats indirectly stimulated at a physiological tetanic frequency (50 Hz). The lowest dose and the instant cisatracurium caused 100% Fade were investigated. Cisatracurium induced 100% Fade 15 min after being administered. Atropine reduced the cisatracurium-induced 100% Fade, but the administration of ZM241385 separately, or combined with atropine, did not cause any effect in the cisatracurium-induced 100% Fade. Data indicate that the simultaneous blockage of M 1 and M 2 muscarinic receptors on motor nerve terminal by atropine is more efficient than the blockage of presynaptic A 2A receptors for a safer recovery of patients from neuromuscular blockade caused by cisatracurium.