This study was designed to evaluate the effects of calcium and potassium channel blockers on local anesthetics-induced vascular relaxation of isolated rat thoracic aorta. In the presence of lidocaine and bupivacaine, the aortic rings previously contracted with phenylephrine(10(-4)M) were slightly contracted at the beginning of the administration of local anesthetics. But in the presence of tetracaine, aortic rings were not contracted at the beginnings. Verapamil, diltiazem and nifedipine in concentration of 10(-9)M to 10(-5)M produced cumulative concentration-dependent vasorelaxation significantly in the aortic rings previously contracted with phenylephrine(10(-4)M). In the presence of lidocaine, bupivacaine and tetracaine, verapamil, diltiazem and nifedipine in concentration of 10(-9)M to 10(-5)M caused dose-dependent vasorelaxation in aortic rings significantly. Tetraethylammonium HCl(TEA) in concentration of 10(-9)M to 10(-5)M did not produce dose-dependent vasorelaxation but slight contraction showed at the beginning of the administration. In the presence of lidocaine, bupivacaine, TEA in concentration of 10(-9)M to 10(-5)M did not produce vasorelaxation remarkably. But in the presence of tetracaine, TEA in concentration of 10(-9)M to 10(-5)M produced cumuIative concentration-dependent vasorelaxation significantly. These findings suggest that local anesthetics, especially tetracaine, which interact with calcium and potassium channel bleckers, lead to blockade of the sodium and calcium channels as well as potassium channels.
Anesthetics, Local ; Animals ; Aorta, Thoracic ; Bupivacaine ; Calcium Channel Blockers ; Calcium Channels ; Calcium* ; Diltiazem ; Lidocaine ; Nifedipine ; Potassium Channel Blockers* ; Potassium Channels* ; Potassium* ; Rats* ; Relaxation* ; Sodium ; Tea ; Tetracaine ; Tetraethylammonium ; Vasodilation ; Verapamil

Even though the relationship between antiarrhythmic drug usage and subsequent prostate cancer (PCa) risk has recently been highlighted, relevant findings in the previous literature are still inconsistent. In addition, very few studies have attempted to investigate the association between sodium channel blockers or potassium channel blockers for arrhythmia and the subsequent PCa risk. Therefore, this cohort study aimed to find the relationship between antiarrhythmic drug usage and the subsequent PCa risk using a population-based dataset. The data used in this study were derived from the Longitudinal Health Insurance Database 2005, Taiwan, China. We respectively identified 9988 sodium channel blocker users, 3663 potassium channel blocker users, 65 966 beta-blocker users, 23 366 calcium channel blockers users, and 7031 digoxin users as the study cohorts. The matched comparison cohorts (one comparison subject for each antiarrhythmic drug user) were selected from the same dataset. Each patient was tracked for a 5-year period to define those who were subsequently diagnosed with PCa. After adjusting for sociodemographic characteristics, comorbidities, and age, Cox proportional hazard regressions found that the hazard ratio (HR) of subsequent PCa for sodium channel blocker users was 1.12 (95% confidence interval [CI]: 0.84-1.50), for potassium channel blocker users was 0.89 (95% CI: 0.59-1.34), for beta-blocker users was 1.08 (95% CI: 0.96-1.22), for calcium channel blocker users was 1.14 (95% CI: 0.95-1.36), and for digoxin users was 0.89 (95% CI: 0.67-1.18), compared to their matched nonusers. We concluded that there were no statistical associations between different types of antiarrhythmic drug usage and subsequent PCa risk.
Adrenergic beta-Antagonists/adverse effects* ; Adult ; Age Factors ; Aged ; Anti-Arrhythmia Agents/adverse effects* ; Calcium Channel Blockers/adverse effects* ; Cohort Studies ; Comorbidity ; Databases, Factual ; Digoxin/adverse effects* ; Humans ; Incidence ; Male ; Middle Aged ; Potassium Channel Blockers/adverse effects* ; Prostatic Neoplasms/epidemiology* ; Retrospective Studies ; Socioeconomic Factors ; Sodium Channel Blockers/adverse effects* ; Taiwan/epidemiology*

Magnesium salts have been reported to be effective in the treatment of atrial, junctional and ventricular arrhythmias resulting from myocardial ischemia, digitalis poisoning, alcoholism, diuretic therapy and coronary artery disease. The mechanism of antiarrhythmic effect is thought to inhibit the efflux of potassium, supress inward sodium movement, and mimic calcium channel blocking drugs by inhibiting cellular calcium uptake. The purpose of this study is to evaluate the antiarrhythmic effect of MgSO4 by inhibiting intracellular calcium transport and dose-related effect. The experiments were composed of four steps. 16 ug/Kg of epinephrine was injected in twenty rabbits anesthetized with halothane (experiment 1). Ventricular arrhythmia was developed in all rabbits. At 15 minutes later, after the retum of sinus rhythm, CaCl2 (10 mg/Kg) was injected slowly for 5 min, and than 16 ug/Kg of epinephrine was injected immediately after the administration of CaC12 (experiment 2). After 45 mins, 8 mg/Kg (experiment 3, n=10) and 16 mg/Kg (experiment 4, n=10) of MgSO4 were injected for 5 mins, and than CaCl2 and epinephrine were administrated as experiment 2. The onset and duration of ventricular arrhythmia following each experiment were observed. The results were as follows; 1) 16 ug/Kg of epinephrine induced ventricular arrhythmia in all cases. 2) CaCl2 infusion caused a reduction in onset and increase in duration of epinephrine-induced-arrhythmia, but there was no significanee. 3) MgSO4-pretreatment caused a increase in onset and reduetion in the CaCl2-caused increase in arrhythmia duration. Only MgSO4-16 mg/Kg values were significant. In conclusion, magnesium salts pretreatment demonstrated effectiveness in preventing ventricular arrhythmia associated with epinephrine usage and hypercalcemic condition during halothane anesthesia.
Alcoholism ; Anesthesia ; Arrhythmias, Cardiac* ; Calcium ; Calcium Channel Blockers ; Coronary Artery Disease ; Digitalis ; Epinephrine* ; Halothane ; Magnesium ; Myocardial Ischemia ; Poisoning ; Potassium ; Rabbits ; Salts ; Sodium

Serotonin is one of the most important neurotransmitters involved in the pathophysiology of depressive illness. The assessment of alteration of cerebral serotonin has been still controversial but interesting topic to study. Recently, increasing evidence has accumulated that the N100 amplitude slope reflects cerebral serotonin activity and treatment response of selective serotonin reuptake inhibitors (SSRIs). We report on two patients who showed abrupt mood changes and side effects after taking SSRI antidepressants. In both patients, aberrantly high N100 amplitude slopes were observed. Our cases suggest that the N100 amplitude slope may be a reliable indicator for predicting manic conversion and side effects in the SSRI treatment of depressive patients. Controlled studies are necessary to confirm whether a high N100 amplitude slope is a useful indicator of SSRI supersensitivity.
Antidepressive Agents ; Depression ; Humans ; Neurotransmitter Agents ; Serotonin ; Serotonin Uptake Inhibitors

This study was designed to identify and characterize Na+ -activated K+ current (I(K(Na))) in guinea pig gastric myocytes under whole-cell patch clamp. After whole-cell configuration was established under 110 mM intracellular Na+ concentration ([Na+]i) at holding potential of -60 mV, a large inward current was produced by external 60 mM K+([K+] degree). This inward current was not affected by removal of external Ca2+. K+ channel blockers had little effects on the current (p>0.05). Only TEA (5 mM) inhibited steady-state current to 68+/-2.7% of the control (p<0.05). In the presence of K+ channel blocker cocktail (mixture of Ba2+, glibenclamide, 4-AP, apamin, quinidine and TEA), a large inward current was activated. However, the amplitude of the steadystate current produced under [K+]degree (140 mM) was significantly smaller when Na+ in pipette solution was replaced with K+ - and Li+ in the presence of K+ channel blocker cocktail than under 110 mM [Na+]i. In the presence of K+ channel blocker cocktail under low Cl- pipette solution, this current was still activated and seemed K+ -selective, since reversal potentials (E(rev)) of various concentrations of [K+]degree-induced current in current/voltage (I/V) relationship were nearly identical to expected values. R-56865 (10-20 microgram), a blocker of IK(Na), completely and reversibly inhibited this current. The characteristics of the current coincide with those of IK(Na) of other cells. Our results indicate the presence of IK(Na) in guinea pig gastric myocytes.
Tetraethylammonium Compounds/pharmacology ; Stomach/*physiology ; Sodium/metabolism/*pharmacology ; Potassium Channels/*physiology ; Potassium Channel Blockers/pharmacology ; Myocytes, Smooth Muscle/*physiology ; Membrane Potentials ; Male ; Guinea Pigs ; Female ; Chlorides/pharmacology ; Calcium/metabolism ; Animals

Randomized trials have shown that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have better safety profiles than classical tricyclic antidepressants (TCAs). However, an increasing number of studies, including meta-analyses, naturalistic studies, and longer-term studies suggested that SSRIs and SNRIs are no less safe than TCAs. We focused on comparing the common side effects of TCAs with those of newer generation antidepressants including SSRIs, SNRIs, mirtazapine, and bupropion. The main purpose was to investigate safety profile differences among drug classes rather than the individual antidepressants, so studies containing comparison data on drug groups were prioritized. In terms of safety after overdose, the common belief on newer generation antidepressants having fewer side effects than TCAs appears to be true. TCAs were also associated with higher drop-out rates, lower tolerability, and higher cardiac side-effects. However, evidence regarding side effects including dry mouth, gastrointestinal side effects, hepatotoxicity, seizure, and weight has been inconsistent, some studies demonstrated the superiority of SSRIs and SNRIs over TCAs, while others found the opposite. Some other side effects such as sexual dysfunction, bleeding, and hyponatremia were more prominent with either SSRIs or SNRIs.
Antidepressive Agents* ; Antidepressive Agents, Tricyclic ; Bupropion ; Depressive Disorder ; Drug-Related Side Effects and Adverse Reactions ; Hemorrhage ; Hyponatremia ; Mouth ; Seizures ; Serotonin and Noradrenaline Reuptake Inhibitors ; Serotonin Uptake Inhibitors

OBJECTIVES: The purpose of this study was to suggest recommendations of antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy. METHODS: Using recommendations from 12 international and domestic clinical practice guidelines for depression, drawing of recommendation drafts, and peer review, the executive committee developed the guideline. RESULTS: Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOI), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRIs), norepinephrine and specific serotonergic antidepressants (NaSSAs), norepinephrine and dopamine reuptake inhibitors (NDRIs), and serotonin antagonist and reuptake inhibitors (SARIs) were strongly recommended as having antidepressant efficacy compared with placebo. Difference in efficacy of antidepressants was as follows. TCAs, MAOI, SSRI, SNRIs, and NaSSAs were strongly recommended, however, NDRIs, SARIs were weakly recommended. If there was no or minimal improvement with treatment, appropriate time of efficacy judgment in antidepressant therapy was estimated to be after two to four weeks. CONCLUSION: We hope that the results of this study will be helpful in encouraging the optimal treatment by understanding antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy.
Antidepressive Agents* ; Antidepressive Agents, Tricyclic ; Depression* ; Depressive Disorder, Major ; Dopamine Uptake Inhibitors ; Judgment* ; Monoamine Oxidase Inhibitors ; Norepinephrine ; Peer Review ; Serotonin ; Serotonin Uptake Inhibitors

To explore novel monoamine reuptake inhibitor with antidepressant activity, a series of substituted aryl alkanol piperidine derivatives were designed and synthesized. All of them were new compounds, and their structures were confirmed with 1H NMR and HR-MS. The results showed that compounds 4, 5 and 8 displayed strong 5-HT, NA and DA reuptake inhibiting activities in vitro. Among the tested compounds, 4, 5 and 13 exhibited potent antidepressant activities in the mice forced swimming test. Compounds 4 and 5 have potent antidepressant activities and are worth further development.
Animals ; Antidepressive Agents ; chemical synthesis ; chemistry ; pharmacology ; Dopamine ; metabolism ; Male ; Mice ; Molecular Structure ; Motor Activity ; drug effects ; Neurotransmitter Uptake Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Norepinephrine ; metabolism ; Piperidines ; chemical synthesis ; chemistry ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Structure-Activity Relationship ; Swimming ; Synaptosomes ; metabolism

Escitalopram is one of the most popular selective serotonin reuptake inhibitors (SSRIs) in current use as a first-line treatment for depression. Escitalopram is well-tolerated and rarely associated with serious side effects. Endocrine and reproductive side effects of serotonergic antidepressants are uncommon and galactorrhea is very rarely mentioned among SSRI-related side effects. Serotonin-enhancing antidepressants may result in a rise in prolactin levels through suppression of dopamine neurotransmission. In the present study, we report a case of hyperprolactinemic galactorrhea associated with escitalopram. A 36-year-old woman developed galactorrhea after initiation of escitalopram for depression and was found to have an elevated prolactin level. Escitalopram was discontinued with resolution of the patient's galactorrhea and normalization of her prolactin level.
Adult ; Antidepressive Agents ; Citalopram ; Depression ; Dopamine ; Female ; Galactorrhea ; Humans ; Pregnancy ; Prolactin ; Serotonin Uptake Inhibitors ; Synaptic Transmission

Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i) was investigated on isolated ventricular myocytes of guinea pig. Single ventricular myocytes were obtained by enzymatic dissociation technique. Fluorescent signal of [Ca2+]i was detected with confocal microscopy after incubation of cardiomycytes in Tyrode' s solution with Fluo3-AM. The result showed that Str increased [Ca2+]i in a concentration-dependent manner. The ventricular myocytes began to round-up into a contracture state once the peak level of [Ca2+]i was achieved in the presence of Str (10 micromol L(- 1)), but remained no change in the presence of Str (1 and 100 nmol L(-1)). Tetrodotoxin (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str (1 and 100 nmol L(-1)) , but had no obvious effects on the action of Str (10 micromol L(-1)). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 micromol L(-1)) or the removal of Ca2+ from Tyrode's solution. In Na+, K+ -free Tyrode' s solution, the response of cardiomycytes in [Ca2+]i elevation to Str (10 micromol L(-1)) was attenuated, while remained no change to Str (1 and 100 nmol L(-1)). TTX, nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str at all of the detected concentrations in Na+, K+ -free Tyrode's solution. The study suggests that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is partially mediated by the extracellular calcium influx through Ca2+ channel or a "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at high (micromolar) concentrations was mainly due to the inhibition of Na+, K+ -ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Aequorin ; pharmacology ; Animals ; Calcium ; metabolism ; Calcium Channel Blockers ; pharmacology ; Calcium Channels ; metabolism ; Fura-2 ; pharmacology ; supply & distribution ; Guinea Pigs ; Myocardium ; pathology ; Nifedipine ; pharmacology ; Ryanodine ; pharmacology ; Sarcolemma ; metabolism ; pathology ; Sarcoplasmic Reticulum ; drug effects ; metabolism ; Sodium-Calcium Exchanger ; Sodium-Potassium-Exchanging ATPase ; antagonists & inhibitors ; Strophanthidin ; pharmacology ; Tetrodotoxin ; pharmacology ; Thapsigargin ; pharmacology