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PubMed1984

Therapy of ventricular tachycardia.

Therapeutic modalities for ventricular tachycardia include antiarrhythmic drugs, direct current cardioversion, electrical pacing and surgical intervention. Lidocaine, procainamide and bretylium are all capable of controlling recurrent ventricular tachycardia; bretylium has the advantage of also being antifibrillatory and of raising the threshold for ventricular fibrillation. Lidocaine and bretylium are available only in i.v. form. Procainamide is available in i.v. as well as oral form. Other oral antiarrhythmic agents include quinidine, disopyramide, beta-blockers such as propranolol and verapamil. The latter may be useful in ventricular arrhythmias induced by ischemia; of these, only beta-blockers appear to significantly raise the threshold for ventricular fibrillation. Control of ventricular ectopy does not always preclude ventricular tachycardia and ventricular fibrillation. In treating ventricular tachycardia, bretylium tosylate is generally given 5 to 10 mg/kg i.v. over 10 to 20 minutes. Given too rapidly, it may cause nausea and vomiting. Orthostatic hypotension, a common side effect, generally abates with continued use and may be ameliorated with tricyclic antidepressants such as protriptyline. Significant supine hypotension may be encountered in patients with acute myocardial infarction and may be managed with pressor agents or fluids, or both. The antiarrhythmic efficacy of bretylium was analyzed in 40 patients. Five etiologic groups were defined by cardiac catheterization: 19 patients had atherosclerotic heart disease, 6 had primary myocardial disease, 4 had mitral valve prolapse, 4 had rheumatic heart disease and 7 had miscellaneous or no heart disease. All patients had recurrent ventricular tachycardia (VT); 23 had ventricular fibrillation (VF) as well. Other antiarrhythmic agents had failed in 38 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Time course of alpha-1-acid glycoprotein and its relation to myocardial enzymes after acute myocardial infarction.

The acute phase reactant, alpha-1-acid glycoprotein, binds to a number of basic antiarrhythmic drugs, including lidocaine, quinidine, propranolol, imipramine and disopyramide. Binding to alpha-1-acid glycoprotein accounts for a decrease in free drug fraction and may alter the expected concentration: response relation of drugs particularly when there are unpredictably large or rapid changes in alpha-1-acid glycoprotein. To determine the time course and magnitude of alpha-1-acid glycoprotein for 1 month after acute myocardial infarction (AMI), blood samples were collected from 27 patients, 14 with AMI and 13 with a chest pain syndrome but no AMI. Patients with AMI had a significant increase in alpha-1-acid glycoprotein after 72 hours (mean 153 +/- 35 mg/dl) (p less than 0.05), and the maximum was observed on day 7 (mean 165 +/- 53 mg/dl) (p less than 0.05), returning to baseline by 28 days. There was no significant change in alpha-1-acid glycoprotein in patients with chest pain but no AMI. Regression analysis showed a significant relation between creatine kinase (p less than 0.005) and lactic dehydrogenase (p less than 0.001) vs alpha-1-acid glycoprotein indicating alpha-1-acid glycoprotein concentration is high in patients with large AMI. Changes in binding resulting from alpha-1-acid glycoprotein during AMI could account for misinterpretation of total drug concentration and response to antiarrhythmic drugs acutely, during convalescence and at discharge.

Adult↗
PubMed1986

Effect of antiarrhythmic therapy on delayed potentials detected by the signal-averaged electrocardiogram in patients with ventricular tachycardia after acute myocardial infarction.

The ability of class I and class II antiarrhythmic drugs to either abolish delayed potentials or modify their timing was investigated in 39 patients with spontaneous ventricular tachycardia (VT) after myocardial infarction. Before the study all patients had delayed potentials on the signal-averaged electrocardiogram and inducible VT with programmed stimulation. These investigations were repeated during 67 trials of oral antiarrhythmic therapy (mexiletine 25, quinidine 24, metoprolol 13, disopyramide 2, procainamide 1, drug combinations 2). Delayed potentials were abolished in only 5 trails (7%), which was within the baseline variability of 8.5% for detection of delayed potentials. In the 7 trials in which VT inducibility was suppressed, delayed potentials persisted in 6 and mean ventricular activation time was virtually unchanged (151 ms before drug therapy, 152 ms after). Quinidine, mexiletine and metoprolol caused no consistent change in ventricular activation time. There was also no change in mean ventricular activation time (164 ms before and 163 ms after drug treatment) in patients in whom spontaneous VT did not recur with drug therapy during follow-up. Thus, the tested antiarrhythmic drugs had no consistent effects on presence or timing of delayed potentials on the signal-averaged electrocardiogram, even when VT inducibility was suppressed or recurrence of spontaneous VT was prevented.

Action Potentials↗
PubMed1986

Basic and clinical cardiac electrophysiology of encainide.

Encainide is a potent sodium channel antagonist. It dissociates slowly from blocked, repolarized channels (time constant of recovery greater than 20 seconds). It markedly slows myocardial and His Purkinje conduction in vitro, in animal models and in humans. In vitro the parent compound and its major metabolites, O-demethyl and 3-methoxy-O-demethyl encainide, have variable effects on action potential duration and refractoriness. In man the parent compound has relatively little effect on refractoriness and QT interval, but its metabolites may increase refractoriness moderately. Encainide has no significant effect on the normal sinoatrial node, and only its metabolites significantly depress atrioventricular nodal conduction and refractoriness. In models of ischemia, all of encainide's actions are more pronounced in ischemic than in normal tissue. Encainide is similar in its basic and clinical electrophysiologic profile to flecainide and lorcainide although its constellation of electrophysiologic properties is unique. It differs from quinidine, procainamide and disopyramide by slowing conduction more and affecting refractoriness less, and by absence of anticholinergic side effects.

Action Potentials↗
PubMed1987

Antiarrhythmic effects of beta-adrenergic blocking agents in benign or potentially lethal ventricular arrhythmias.

Classification of ventricular arrhythmias into those that are benign, potentially lethal and lethal is based on their associated risk for producing sudden cardiac death. This classification system is useful in defining indications for the treatment of ventricular arrhythmias and predicting differential rates of antiarrhythmic drug efficacy and toxicity. Whether the reduction of potentially lethal ventricular arrhythmias will prevent sudden cardiac death remains to be determined. The class II antiarrhythmic agents--the beta-adrenergic blocking drugs--have been shown to reduce sudden cardiac death in postmyocardial infarction patients, but the precise mechanism of their effect has not been defined. beta blockers are efficacious in approximately 50% of patients with benign or potentially lethal ventricular arrhythmias. This response is comparable to that seen with the class IA agent disopyramide or the class IB agents tocainide and mexiletine. beta blockers have favorable side-effect profiles including a low incidence of proarrhythmia and a lack of organ toxicity such as hepatitis, pulmonary fibrosis or agranulocytosis, which are concerns with class I and class III antiarrhythmic drugs. The proper dosage of the beta blocker is critical in limiting adverse effects. In a study of 23 patients with benign or potentially lethal ventricular arrhythmias, 11 (48%) of the patients responded to nadolol with a reduction of greater than 75% in arrhythmia frequency, and several patients responded at nadolol dosages as low as 10 mg daily. Thus, it is plausible to consider beta blockers as first-choice antiarrhythmic therapy, even in patients with left ventricular dysfunction when sympathetic tone is not required to maintain cardiac compensation.

Adolescent↗
PubMed1988

Overview of the clinical pharmacology of antiarrhythmic drugs.

Antiarrhythmic drugs have been recognized to possess 1 or more classes of antiarrhythmic action. This classification scheme is useful, but has major limitations because the available drugs and their metabolites have multiple actions. This report presents an overview of the distinguishing features of the most frequently used agents having class I or III actions. Agents with class I actions are local anesthetic agents that depress the fast inward depolarizing sodium current and thereby slow the rate of the rise of the action potential (phase 0). This category is further divided into classes IA, IB, and IC according to the degree of potency as sodium channel inhibitors, and the individual effects of the drug on action potential, conduction velocity and repolarization. Included in the spectrum of agents with class I action are quinidine, procainamide, disopyramide, lidocaine, tocainide, mexiletine, flecainide, amiodarone, encainide and lorcainide. The antiarrhythmic drugs that exert class III action lengthen repolarization and refractoriness; included in this category are amiodarone, quinidine, bretylium and sotalol. Because of the broad range of effects that antiarrhythmic agents may exert, safe and effective therapy requires a thorough familiarity with the pharmacologic profile of each drug administered and a careful evaluation of the presenting condition and the patient history. In some cases, a multiple drug regimen may be most appropriate. Various combinations such as class IA and IB agents, have been shown to slow conduction synergistically and increase refractoriness while keeping adverse effects to a minimum.

Action Potentials↗
PubMed1988

Chronic ventricular arrhythmias: which drug for which patient?

Many agents, including a number of drugs recently approved by the Food and Drug Administration, are now available for the treatment of chronic ventricular arrhythmias. The so-called first-generation agents--quinidine, procainamide and disopyramide--have been used in large numbers of patients for many years, and the safety and efficacy profiles of these drugs are well established. The "second-generation" antiarrhythmic agents recently approved by the Food and Drug Administration offer promising new alternatives; however, their safety and efficacy profiles have yet to be confirmed for broad populations over extended periods of time. Although it is recognized that the choice of agent for treatment of a particular patient is a "therapeutic trial," with an unpredictable outcome of efficacy and adverse effects, certain "descriptors," such as patient age or co-existing medical conditions, are often helpful in determining which agent is most likely to be clinically effective, and which agents are most likely to produce adverse effects. When other medical conditions such as hepatic or renal failure are present, the appropriate choice of drug and dosage is required for optimal management of the arrhythmia and for prevention of overdosage, exacerbation of other medical problems and deleterious interactions. Combination therapy with multiple antiarrhythmic agents is often quite effective for increasing arrhythmia control without increasing adverse effects. However dosage modifications are often necessary when an antiarrhythmic drug is given in conjunction with another such agent, or with agents that also have electrophysiologic activity or modify metabolic or elimination functions. The following report is one clinician's approach for optimizing efficacy and minimizing toxicity while using the difficult class of drugs called antiarrhythmic agents. It will encourage the use of certain drugs before others, based on considerations of efficacy, safety, ease of administration, follow-up, and other factors.

Adult↗
PubMed1989

Evaluation of antifibrillatory effects of drugs.

Several electrical stimulation techniques have been used to measure ventricular fibrillation (VF) threshold such as single pulse stimulation, train of pulses stimulation, continuous 50-Hz stimulation and sequential pulse stimulation. This study was undertaken to clarify the difference in VF threshold values obtained by each method. The development of VF was classified into 4 stages. Stage 1 is the phase in which fragmented activities are generated at the stimulated area of the ventricular muscle. In stage 2, the local activities propagate to surrounding ventricular muscle, causing ventricular excitation. Stage 3 is characterized by repetitive ventricular excitations. In state 4, repetitive ventricular responses in a form of accelerating tachycardia induce disorganized excitations that finally degenerate into fibrillation. Based on this classification of stages between local excitation and fibrillation, single pulse stimulation is considered to measure VF threshold for stages 1 to 4, continuous 50-Hz stimulation for stages 2 to 4 and sequential pulse stimulation for stages 3 and 4. Thus, the antifibrillatory effect of drugs can be interpreted with some significance by using different stimulation methods. The sequential pulse stimulation method revealed that some antiarrhythmic agents caused a dissociation between repetitive nonstimulated excitation (RE) threshold and VF threshold. Procainamide and disopyramide increased RE threshold while decreasing VF threshold. Mexiletine and lidocaine elevated both RE and VF thresholds. Local infusion of procainamide at the site of test stimulation reduced both thresholds. However, after the application of procainamide to the whole heart, RE threshold remained decreased but VF threshold was elevated. It is likely that the antifibrillatory effect of the drug includes 2 different processes: antireentrant and antimultiple reentrant effects.

Animals↗
PubMed1989

Differentiation and mechanisms of prevention and termination of verapamil-sensitive sustained ventricular tachycardia.

The purpose of this study was to differentiate by means of electrophysiologic study, a drug's ability to terminate or to prevent ventricular tachycardia (VT). Differences between the 2 effects were examined in patients with VT and the underlying mechanisms were studied in verapamil-responsive idiopathic sustained VT. The clinical significance of the distinction for chronic oral drug therapy is discussed. Thirty-five cases of inducible sustained VT were studied. A drug was considered "preventive" if it prevented VT induction and repetitive ventricular response, and "terminating" if it stopped induced VT within 15 complexes or could stop VT after its intravenous administration. Prevention and termination occurred together in 13 of 19 cases (68%) with disopyramide, in 10 of 19 cases (53%) with procainamide, in 8 of 12 cases (67%) with lidocaine, in 11 of 15 cases (73%) with mexiletine, and in 10 of 16 cases (63%) with verapamil. In the 16 in which verapamil terminated VT, VT rate immediately before termination slowed markedly from 167 +/- 33 to 134 +/- 28 beats/min. In the 6 cases without preventative effects, minimal and maximal premature intervals for VT induction increased significantly, from 291 +/- 70 to 335 +/- 85 ms and 323 +/- 68 to 423 +/- 109 ms, respectively, after verapamil administration. In 2 cases in which verapamil had a terminating effect, 5 mg of verapamil restored sinus rhythm but 10 mg caused premature beats resembling VT complexes. In another 2, 5 mg of verapamil lengthened the minimal premature interval; 10 mg increased both minimal and maximal premature intervals and lengthened the VT cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Risk-benefit profiles of antiarrhythmic therapy.

Whereas much has been learned of the mechanisms and pathophysiology of cardiac arrhythmias, treatment remains controversial and is largely empiric. Cardiac arrhythmias range in severity from innocuous to fatal; antiarrhythmic agents offer differing degrees of efficacy, inefficacy or toxicity. For an arrhythmia that needs treatment, there is no reliable or easy method for selecting the most appropriate antiarrhythmic drug. Antiarrhythmic treatment is justified for arrhythmias that are symptomatic or hemodynamically significant, the risk of lethality dictating the degree of drug toxicity that might be tolerated. The treatment of prognostically important arrhythmias is indicated if their suppression is rewarded by an improved prognosis. However, these arrhythmias are often merely indicators of a bad prognosis rather than the cause of death. Assessment of the risk-benefit ratio of antiarrhythmic treatment principally depends on the perceived risk and symptomatology of the arrhythmia and the efficacy and toxicity of the antiarrhythmic drug. Beta-adrenoceptor blocking drugs offer optimal risk-benefits for the prevention of ventricular fibrillation (infarct survivors and long QT syndrome); disopyramide and the class IC agents offer acceptable risk-benefit ratios for the treatment of ventricular tachycardia, whereas no antiarrhythmic drug offers an acceptable risk-benefit for the suppression of asymptomatic "cosmetic" atrial or ventricular ectopic beats.

Anti-Arrhythmia Agents↗
PubMed1990

Day-to-day reproducibility of antiarrhythmic drug trials using programmed extrastimulus techniques for ventricular tachyarrhythmias associated with coronary artery disease.

Forty-nine patients with coronary artery disease and documented clinical sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) were studied twice in the drug-free state and twice during treatment with an identical antiarrhythmic medication at therapeutic plasma concentrations using an identical programmed electrical stimulation protocol. Tested drugs included procainamide, quinidine, disopyramide and phenytoin. During their 2 paired tests, 11 patients had nearly identical therapeutic plasma concentrations of antiarrhythmic agents (group I) and 38 patients had therapeutic plasma concentrations, but with more variation in drug levels between otherwise identical paired drug tests (group II). Overall, 71% of patients had inducible sustained VT or VF during drug testing. Induced ventricular arrhythmias were not reproducible in 45% of group I patients, despite restudy at nearly identical therapeutic plasma concentrations of an identical antiarrhythmic agent. Induced arrhythmias were also not reproducible in 16% of group II patients. This variability could not be attributed to the electrophysiologic characteristics of the patients studied. Drug trials directed by programmed stimulation should be cautiously interpreted because time-associated changes can mimic a change attributed to a beneficial or deleterious drug effect.

Anti-Arrhythmia Agents↗
PubMed1990

Effectiveness of propranolol added to a type I antiarrhythmic agent for sustained ventricular tachycardia secondary to coronary artery disease.

The effect of adding propranolol to procainamide, quinidine, propafenone or disopyramide was prospectively evaluated in 37 patients, all with prior infarction and inducible ventricular tachycardia (VT). After showing that VT remained inducible during therapy with a type I drug, 23 patients received intravenous propranolol. The ventricular effective refractory period, prolonged by the type I agent, was further increased by propranolol. The cycle length of the VT also increased after the type I drug and propranolol exaggerated this effect. Seven of the 23 patients were rendered noninducible after propranolol and another 10 manifested a greater than 100 ms increase in induced VT cycle length. In the other 14 patients, propranolol was infused immediately after the basal study. If VT remained inducible, testing was repeated after a type I drug was added. The ventricular effective refractory period, as well as the VT cycle length, increased after propranolol and was further prolonged after the addition of a type I agent. Seven of these 14 patients were rendered noninducible, 3 with propranolol alone and 4 others with the combination, and in 4, the VT cycle length was prolonged by greater than 100 ms. A total of 17 patients were discharged on either propranolol alone (3 patients) or on an effective combination (14 patients). During a mean follow-up of 20 months, 1 patient died suddenly, 2 had recurrence of well-tolerated VT and 9 remain on therapy. Thus, propranolol has a demonstrable antiarrhythmic effect in the invasive laboratory and may supplement the antiarrhythmic efficacy of conventional type I antiarrhythmic drugs.

Aged↗
PubMed1993

Serial electropharmacologic studies in patients with ischemic heart disease and sustained ventricular tachyarrhythmias: when is drug testing sufficient?

Serial testing of antiarrhythmic drugs by programmed electrical stimulation can be costly in time, expense and risk. The purpose of this study was to evaluate the results of serial electropharmacologic tests for similarities that might obviate the need for protracted drug testing. Serial electropharmacologic testing was performed in 283 patients with coronary artery disease and clinical sustained ventricular tachycardia (VT) or fibrillation (VF). Drug tests were defined as concordant if sustained VT or VF could be consistently induced, or failed to be consistently induced during all such trials in a given patient. The following drugs were included for testing: procainamide, quinidine and disopyramide (class IA); phenytoin, mexiletine and tocainide (class IB); and flecainide and encainide (class IC). All patients were serially tested with > or = 2 (mean and median, 3) antiarrhythmic agents regardless of results from drug-free testing or initial acute drug testing. Overall, the results of serial drug trials directed by programmed stimulation were concordant in more than two thirds of patients. Concordance was comparably high whether patients were serially tested with drugs within the same antiarrhythmic class, or with drugs from differing classes, and was not related to patients' clinical or electrophysiologic characteristics. Protracted serial electropharmacologic testing does not appear necessary for predicting successful or unsuccessful antiarrhythmic drug therapy in survivors of clinical VT or VF. Single drug testing can identify most patients whose arrhythmia will or will not respond to medications.

Action Potentials↗
PubMed1995

Relevance of asystole during head-up tilt testing.

The prognosis of patients manifesting prolonged asystole during head-up tilt testing is unclear. In 209 consecutive patients with a history of syncope and positive head-up tilt tests, 19 had asystole lasting > 5 seconds (mean duration 15 +/- 10) (group 1a). When compared with patients without asystole (group 1b), group 1a patients were younger (32 +/- 12 vs 47 +/- 21 years, p < 0.005), but clinical manifestations were not any more dramatic (the number of episodes of syncope [7 +/- 5 vs 8 +/- 6 episodes, p = NS] and injury during syncope [2 vs 13 patients, p = NS] were similar). During follow-up (mean 2 +/- 1 year), with the patient taking pharmacologic therapy such as beta blockers, ephedrine, theophylline, or disopyramide, the recurrence rate was 11% and 8% in groups 1a and 1b (p = NS). No patient in the asystole group underwent pacemaker implantation. Additionally, of 75 normal volunteers (group 2) with no history of syncope undergoing tilt tests to define its specificity, 3 had asystole (mean duration 10 seconds). During > 1 year of follow-up, despite no treatment, all 3 are symptom free. Thus, asystole during head-up tilt testing does not predict either a more malignant outcome or a poor response to pharmacologic therapy. Moreover, an asystolic response does not enhance the specificity of the head-up tilt test because it may be present in asymptomatic "normal" volunteers.

Adolescent↗
PubMed1988

Effects of basic drugs on the hepatic transport of cardiac glycosides in rats.

The effects of some basic and acidic drugs on the hepatic uptake of digoxin and ouabain were studied in isolated rat hepatocytes. Digoxin accumulated against a concentration gradient, and its initial uptake was energy- and temperature-dependent. Digoxin competitively inhibited the uptake of ouabain (Ki = 1.3 microM), which was reported to be transported by a carrier-mediated active transport system. All basic drugs tested (verapamil, dipyridamole, amiodarone, nifedipine, diltiazem, ajmaline, chlorpromazine, imipramine, disopyramide, quinidine, procainamide, propranolol and lidocaine: 50 microM) except for procainamide, propranolol and lidocaine significantly (P less than 0.05) reduced the uptake of digoxin, whereas acidic drugs (salicylic acid and phenytoin) had no effect. The same inhibitory effects were observed for ouabain uptake, whereas the uptake of alanine was not changed by these drugs. Quinidine inhibited the uptake of ouabain in a noncompetitive manner (Ki = 88 microM). These basic drugs had no effect on the permeability of the cells assessed by the trypan blue exclusion test and succinate-simulated oxygen consumption. But carbonylcyanide-m-chlorophenyl hydrazone-stimulated oxygen consumption decreased in the presence of some basic drugs and correlated with their inhibitory effects on digoxin uptake. Therefore, one of the mechanisms of the inhibitory effects of these drugs on digoxin uptake was the inhibition of oxidative phosphorylation. These basic drugs had no effect on the microtubular system, which was assessed by the measurement of tubulin polymerization and colchicine binding to tubulin. The results of our study suggested that many basic drugs have a potential to inhibit the hepatocellular uptake of cardiac glycosides.

Animals↗
PubMed1990

Inhibitory studies of mexiletine and dextromethorphan oxidation in human liver microsomes.

The cytochrome P-450dbl isozyme (P-450bdl) is responsible for the genetic sparteine-debrisoquine type polymorphism of drug oxidation in humans. To investigate the relationship between mexiletine oxidation and the activity of this isozyme, cross-inhibition studies were performed in human liver microsomes with mexiletine and dextromethorphan, a prototype substrate for P-450dbl. The formation of hydroxymethylmexiletine and p-hydroxymexiletine, two major mexiletine metabolites, was competitively inhibited by dextromethorphan. Mexiletine competitively inhibited the high affinity component of dextromethorphan O-demethylation. In addition, there was a good agreement between the apparent Km values for the formation of both mexiletine metabolites and the high affinity component of dextromethorphan O-demethylation and their respective apparent Ki values. Several drugs were tested for their ability to inhibit mexiletine oxidation. Quinidine, quinine, propafenone, oxprenolol, propranolol, ajmaline, desipramine, imipramine, chlorpromazine and amitryptiline were competitive inhibitors for the formation of hydroxymethylmexiletine and p-hydroxymexiletine as for prototype reactions of the sparteine-debrisoquine type polymorphism. Amobarbital, valproic acid, ethosuximide, caffeine, theophylline, disopyramide and phenytoin, known to be non-inhibitors of P-450dbl activity, were found not to inhibit the formation of these mexiletine metabolites. Moreover, the formation of both metabolites was strongly inhibited by an antiserum containing anti-liver/kidney microsomes antibodies type I (anti-LKMI) directed against P-450dbl. These data suggest that the formation of two major metabolites of mexiletine is predominantly catalysed by the genetically variable human liver P-450dbl.

Binding, Competitive↗
PubMed1994

Methadone: a potent inhibitor of rat liver aldehyde oxidase.

Several drugs with structural similarities to SKF-525A were tested for their ability to inhibit rat liver aldehyde oxidase using the experimental antitumour agent N-[(2'-dimethylamino)ethyl]acridine-4-carboxamide (AC; NSC 601316; acridine carboxamide) as substrate. The antihistamine D-chlorpheniramine, and the antiarrhythmics disopyramide, procainamide and lignocaine were ineffective in inhibiting this reaction. The antihistamines diphenhydramine, pheniramine, doxylamine, orphenadrine, methapyrilene and pyrilamine, gave IC50 values of 100-500 microM. The narcotic analgesics D-propoxyphene and, in particular, methadone were potent inhibitors of acridine formation with IC50 values of 15.5 and 0.31 microM, respectively. Further analysis indicates mixed non-competitive type inhibition by methadone with inhibition constants (Kis and Kii, respectively) of 0.03 +/- 0.01 (SE) and 0.57 +/- 0.12 microM.

Acridines↗
PubMed1989

Effect of drugs on histamine radio-enzyme assay.

The effect of over 200 drugs and other compounds on histamine radio-enzyme assay was studied. Some muscle relaxants (e.g. alcuronium), some sympathomimetics (e.g. dopamine, isoxsuprine, tyramine and possibly phenylethylamine), antimalarial drugs, procaine, procainamide, Berenil and serotonin were potent compounds to interfere with this assay. In some special cases still potentially inhibitory drugs seemed to be some muscle relaxants (e.g. vecuronium, pancuronium and tubocurarine), antidepressants, antihistamines (e.g. cimetidine, ranitidine and diphenhydramine), chinidin, disopyramide, tolazoline and salazosulfapyridine.

Histamine↗