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PubMed1990

A simulation of neuromuscular function and heart rate during induction, maintenance, and reversal of neuromuscular blockade.

We developed a two-compartment model to simulate neuromuscular function and heart rate following the administration of four nondepolarizing neuromuscular blocking agents (atracurium, vecuronium, pancuronium, and d-tubocurarine), three neuromuscular block reversal agents (edrophonium, neostigmine, and pyridostigmine), and two anticholinergic agents (atropine and glycopyrrolate). Twitch depression, train-of-four ratio, and heart rate were modeled during fentanyl, halothane, enflurane, or isoflurane anesthesia, optionally supplemented with nitrous oxide. Simulation results, compared with published values for each drug, fell within the clinical accuracy range (onset time 6.1 +/- 3.9% [mean +/- SEM]; duration, 1.7 +/- 3.5%, 50% effective dose, 0.5 +/- 5.7%; and 95% effective dose, 2.1 +/- 1.1%). The simulation graphically demonstrates the pharmacokinetics, pharmacodynamics, and interactions between neuromuscular blocking agents, reversal agents, and anticholinergic agents. During a simulation, the need for frequent monitoring and repeated delivery of a neuromuscular blocking agent to keep neuromuscular blockade stable becomes apparent, especially with the intermediate-acting neuromuscular blocking agents. When inhalational agents are given concomitantly, the task becomes even more difficult, since potentiation changes with anesthetic uptake. Recurarization, tachycardia, or bradycardia may be seen with the simulation if an improper drug regimen is followed. Concurrent simulation of two identical patients allows comparison of different modes of administration, choice of anesthetic agents, and drug doses.

Administration, Inhalation↗

PubMed1991

Split-dose atropine versus glycopyrrolate with neostigmine for reversal of gallamine-induced neuromuscular blockade.

The effects of a split-dose of atropine sulphate versus a single dose of glycopyrrolate given with neostigmine for the reversal of gallamine-induced neuromuscular blockade were studied in 55 patients undergoing gynaecological surgery. The patients were randomized to receive either a single dose of glycopyrrolate (7 micrograms.kg-1) or two doses of atropine (8 micrograms.kg-1 each), given with an interval of 1 min. There were no differences between the two methods with respect to percentage heart rate changes, salivation or arousal time. Four patients demonstrated cardiac arhythmias in the atropine group, whereas none occurred in the glycopyrrolate group (P less than 0.05). It is concluded that a split-dose of atropine has similar chronotropic effects to a single dose of glycopyrrolate for the reversal of gallamine-induced neuromuscular blockade. However, the finding of a higher incidence of cardiac arrhythmias in the atropine group suggests that this reversal regime should be reserved for patients without cardiac disease.

Adult↗

PubMedDate not supplied

[Intubation with propofol without neuromuscular blockade. Effect of premedication on fentanyl and lidocaine].

AIMS: Laryngotracheal reflexes, and possibilities of intubations following anaesthetic induction with propofol, with or without premedication and without neuromuscular blockade were evaluated. Hemodynamic parameters were also measured. METHODS: Sixty ASA I-II patients were randomly allocated into 3 groups according to anaesthetic premedication. Group P: (placebo), 2 and 4 ml of saline 0.9%; group F, 4 micrograms/kg of fentanyl and 2 ml of saline 0.9%; group L, 4 micrograms/kg of fentanyl and 1.5 mg/kg of lidocaine 5%. Two point five mg/kg of propofol were administered and 45 seconds later intubation was attempted. Mandibular relaxation, visualization of the glottis, opening of the vocal chords, reflex reactions to laryngoscopy and intubation, time used, blood pressure and heart rate were evaluated. RESULTS: Mandibular relaxation and visualization of the glottis were acceptable in all the patients. The aperture of the vocal chords was enough so as to carry out intubation in 65% (P), 100% (F) (p < 0.05) and 95% (L) (p < 0.05). Laryngeal reactivity significantly decreased (p < 0.001) from 40% (P) to 15% (F) and 10% (L). Tracheal reflexes decreased from 84.6% (P) to 55% (F) (p < 0.01) and 37% (L) (p < 0.001). Blood pressure and heart rate rose with intubation over the basal levels in group P and significantly decreased in groups F and L. CONCLUSIONS: The use of propofol without neuromuscular blockade is inadequate for intubation since laryngotracheal reflexes are not suppressed. Besides, propofol does not prevent hemodynamic reactions. Premedication with fentanyl and/or lidocaine improves the responses not sufficiently to safely perform intubation.

Adult↗

PubMed1990

Effect of volatile anesthetics on vecuronium-induced neuromuscular blockade in children.

We studied 60 children undergoing elective surgery to evaluate the effect of interactions between vecuronium and isoflurane or halothane on the potency and duration of neuromuscular blockade, as measured by electromyography. Vecuronium was first administered by a logarithm-based cumulative method (14, 22, 35, 56, 89 micrograms/kg) in 10 children anesthetized with thiopental (5 mg/kg), alfentanil (15 micrograms/kg first dose, then 10 micrograms/kg), and N2O/O2 (60:40) until a 95% +/- 2% twitch depression (ED95) was obtained. Thirty children given the same balanced anesthesia were then randomly assigned to three groups (n = 10 in each) to receive a single ED20 (21 micrograms/kg), ED50 (33 micrograms/kg), or ED80 (47 micrograms/kg) intravenous bolus of vecuronium calculated from the mean regression line of twitch responses of the first 10 children. In the second part of the study, 20 children were anesthetized with isoflurane (1.2%) or halothane (0.7%) and compared with the previous 10 children anesthetized with alfentanil-N2O. Potency of vecuronium determined by single-bolus or logarithm-based cumulative techniques was not significantly different. Isoflurane and halothane significantly decreased ED50 (22.3 +/- 1.6 and 25.4 +/- 1.4 micrograms/kg, respectively; mean +/- SE) and ED95 (41.5 +/- 3.3 and 46.7 +/- 3.2 micrograms/kg, respectively) compared with alfentanil-N2O (ED50: 32.8 +/- 0.8 micrograms/kg, ED95: 70.5 +/- 2.6 micrograms/kg). Recovery rate from vecuronium-induced neuromuscular blockade was significantly longer with isoflurane than with alfentanil-N2O or halothane. We conclude that in children single-bolus and logarithm-based cumulative techniques give similar potency estimates for vecuronium. Isoflurane and halothane increase by similar amounts the neuromuscular potency of vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗

PubMed2004

An anaesthetic protocol in the young domestic pig allowing neuromuscular blockade for studies of cardiac function following cardioplegic arrest and cardiopulmonary bypass.

BACKGROUND: Neuromuscular blockade should, for ethical reasons, not be allowed in animal experiments unless the use is strongly motivated. Beforehand, the anaesthetic protocol must be documented without muscle relaxation in the species studied. Documentation is difficult to obtain from the scientific literature. When focusing on cardiac function over time, in particular, the ideal anaesthetic protocol should cause no or minor alterations in cardiac variables. METHODS: We intended to document an anaesthetic protocol involving ventilation with N(2)O combined with loading doses and continuous infusions of pentobarbital, fentanyl and midazolam in seven pigs by applying potentially painful stimuli every 15 min for 7 h. Subsequently, left ventricular global and regional function was studied with conductance catheter and strain rate imaging by echocardiography in eight pigs with pancuronium included. RESULTS: Pigs without pancuronium were completely immobilized and unresponsive to potentially painful stimuli and sternotomy, with no accumulation or degradation of anaesthetic agents. With pancuronium included, left ventricular preload gradually decreased together with reduction of cardiac index from 3.52 +/- 0.14 at 2 h to 2.84 +/- 0.11 L min(-1). m(-2) (+/-SEM) after 7 h of observation. Preload recruitable stroke work decreased after 7 h, whereas peak systolic strain in the anterior left ventricular wall and load-independent indices of diastolic function were not significantly altered. CONCLUSION: In specific experimental protocols, the anaesthetic protocol described could allow the use of muscular paralysis in young domestic pigs, for instance when involving hypothermic cardiopulmonary bypass, cardioplegic arrest and reperfusion.

Adjuvants, Anesthesia↗

PubMed2006

A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome.

BACKGROUND: Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? METHODS: The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. RESULTS: Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5%-95% percentiles $42,259-$83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. CONCLUSION: ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS.

Computer Simulation↗

PubMed2004

Sedation, analgesia, and neuromuscular blockade in sepsis: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for sedation, analgesia, and neuromuscular blockade in sepsis that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: There is no preferred sedative or analgesic agent for use in the critically ill septic patient during mechanical ventilation. Protocols should be utilized for administration of sedation with predefined sedation scale targets. Either intermittent bolus sedation or continuous infusion sedation to predetermined end points with daily interruption/lightening of continuous infusion sedation with awakening and re-titration, if necessary, are recommended. Neuromuscular blockade should be avoided if possible and, if used continuously, requires twitch monitoring.

Analgesics↗

PubMed1999

[Development of a new closed-loop system for controlling mivacurium-induced neuromuscular blockade].

UNLABELLED: There are many closed-loop control systems for muscle relaxants reported, but only a few could cope with the introduction of the latest shorter acting neuromuscular blocking drugs. These new muscle relaxants such as mivacurium require a fast adapting closed-loop system for controlling an adequate infusion. METHODS: After approval of the local ethics committee and having the patients' informed consent a total number of 75 patients [ASA I and II] were included in the study and assigned either to a training-, prediction-, prediction-/feedback- or a validation phase, as needed. Anaesthesia was induced and maintained with propofol in a TCI-mode with a plasma level of 3 to 5 micrograms/ml and 0.1 mg fentanyl boli as needed in all patients. In the last validation phase, having 20 patients, the prediction error and the error of the whole system was taken and analysed. RESULTS: A closed-loop system using a neural network as a predictor could be established. In the final validation phase consisting of 20 patients the mean square prediction error was found to be 0.1% +/- 0.2% [mean +/- SD]. The mean square error of the whole system was 0.55% +/- 0.59% [mean +/- SD]. CONCLUSIONS: A closed-loop system for control of a mivacurium infusion could be established. The system proofed to be reliable for a closed-loop infusion of mivacurium in order to maintain a predefined degree of neuromuscular blockade of 95% during routine surgery. The performance of the described controller is comparable to all recent attempts and could therefore be useful for scientific studies. It should be further validated and established for other muscle relaxants, as well.

Adolescent↗

PubMed1992

[Nifedipine prolongs a neuromuscular blockade caused by atracurium].

Calcium entry blockers are now widely employed in the treatment of cardiovascular diseases and perioperative hypertension. In patients with coronary heart disease nifedipine therapy should be continued perioperatively to avoid coronary artery spasm. Animal experiments have demonstrated that calcium entry blockers potentiate the neuromuscular blockade induced by nondepolarizing blocking agents. In patients, an atracurium-induced neuromuscular depression is prolonged by intravenous nifedipine. In this prospective clinical study we evaluated the effect of chronic oral nifedipine therapy on the duration of neuromuscular block by atracurium. Sixty patients anaesthetized with isoflurane in nitrous oxide/oxygen were recruited for this study. Thirty of these were on chronic oral nifedipine therapy and received their normal morning dose before premedication. The control consisted of 30 patients of similar age and status but not taking any calcium entry blockers. Monitoring included noninvasive blood pressure, heart rate, pharyngeal temperature, physical breathing parameters and neuromuscular transmission with a Datex Relaxograph TM ("train of four"-principle). After inducing hypnosis 0.5 mg/kg atracurium were administered for muscular relaxation. The duration of block from administration of the relaxant to recovery of first twitch height (T1) to 25% of control twitch height was registered as duration of initial block. When T1 reached 25% a repetition dose of 0.2 mg/kg atracurium was injected. The time till recovery of T1 to 25% was recorded as the duration of the repetition dose. Results were compared using Student's t-test for unpaired data. There was a significant prolongation of the duration of initial block from 38 min +/- 10 min in the control group to 46 min +/- 8 min in the therapy group (P < 0.01). The duration of the repetition dose rose from 30 min +/- 8 min in the control group to 38 min +/- 7 min in the therapy group (P < 0.001). Daily nifedipine doses varied from 10 mg in the morning to 40 mg divided into single doses with no influence on the prolongation of neuromuscular block. Our results confirm previous assumptions of synergistic effects of nifedipine and neuromuscular blocking drugs in patients. Chronic oral nifedipine therapy potentiates neuromuscular blockade by atracurium as does nifedipine intravenously. This effect should be considered in the treatment of cardiovascular diseases with nifedipine in the perioperative period.

Aged↗

PubMed1984

Evaluation of peripheral nerve stimulators and relationship to possible errors in assessing neuromuscular blockade.

Voltage and current output characteristics were measured on six commercially available peripheral nerve stimulator devices. The results are evaluated as possible sources of variability in peripheral nerve stimulator function and neuromuscular blockade assessment. The authors found significant differences in output voltage waveform and in maximum current into a 470 ohm load (21.4 to 128 mA.). Output current decreased from 25 to 88% in the different devices, with a load impedance increase from 470 to 10,000 ohms. Due to the variability in peripheral nerve stimulation units and the decrease in current output at higher load impedance, less than supramaximal stimulation is possible with erroneous interpretation of neuromuscular blockade.

Electric Stimulation↗

PubMed1986

Antagonism of profound neuromuscular blockade induced by vecuronium or atracurium. Comparison of neostigmine with edrophonium.

The effectiveness of neostigmine 0.07 mg kg-1 and edrophonium 0.8 mg kg-1 as antagonists of profound neuromuscular blockade induced by vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 was studied in 59 healthy patients. The antagonists were administered 5 min after total ablation of the twitch response and the end-point of recovery was a train-of-four ratio of 70%. In 30 patients given vecuronium the mean time to reach this point (duration TOF70) was 66.7 min in the control group (no antagonist), 43.5 min in the group given neostigmine and 59.8 min in the group given edrophonium. The duration TOF70 was shorter in the neostigmine group than in the control (P less than 0.01) and edrophonium (P less than 0.01) groups. The duration TOF70 did not differ from control in the edrophonium group. In 29 patients given atracurium, the durations TOF70 were 66.4, 44.1 and 54.9 min in the control, neostigmine and edrophonium groups, respectively. The durations TOF70 in the neostigmine (P less than 0.01) and edrophonium (P less than 0.01), groups were shorter than control. The duration TOF70 of the neostigmine group was shorter than in the edrophonium group (P less than 0.01). These results show that profound neuromuscular blockade cannot be rapidly antagonized by either of these two agents, but if reversal is required under these circumstances, neostigmine would be the more effective drug.

Adult↗

PubMed1993

Isoflurane and mivacurium chloride neuromuscular blockade in patients with myasthenia gravis.

The relaxograph findings are presented in two patients. In the first, isoflurane alone is administered, and mivacurium with isoflurane is administered to the second patient with myasthenia gravis. A significantly lower dose of mivacurium is required. It was noticed that the T4:T1 ratio was 100% after mivacurium and reversal agent, but T1 did not return to normal. In the patient that only received isoflurane, T1 was 60% to 70% of the baseline, indicating the neuromuscular blocking effects of isoflurane. These cases illustrate that inhalation anesthetics are adequate for muscle relaxant effects, and if neuromuscular blockers are necessary, then a lower dose of nondepolarizer should be administered, and the patient carefully monitored. Mivacurium appears to be an ideal agent for neuromuscular blockade in myasthenia gravis as long as careful neuromuscular blockade is performed.

Adult↗

PubMed1985

Assessment of neuromuscular blockade produced by atracurium in frog sartorius muscle.

The neuromuscular effects of atracurium in frog sartorius muscle were studied and the results were compared with those obtained by tubocurarine in the same preparation. Single twitch (at 1 per 5 s) and tetanic stimulation (at 1-100 per s) of the motor nerve, stimulated with 5-10 V (maximum) and 0.2 ms pulse duration, were used to assess the neuromuscular blockade produced by atracurium and tubocurarine in the frog sartorius muscle. The results showed that atracurium was twice as potent as tubocurarine in reducing the amplitude of the indirectly-elicited twitch contractions in the frog sartorius muscle. The mean IC50 values (concentration to produce 50% inhibition of twitch tension) of atracurium and tubocurarine-induced depression of the indirectly-elicited twitch tension were 0.64 +/- 0.1 microM and 1.2 +/- 0.2 microM respectively (means +/- s.e., n = 6, P less than 0.001). Furthermore, atracurium had a shorter time of onset, time to 50% block and time to 95% recovery than tubocurarine.

Animals↗

PubMed1984

Neuromuscular blockade enhances phrenic nerve activity during high-frequency ventilation.

Phrenic nerve activity was monitored in anesthetized cats during high-frequency ventilation (HFV). Rhythmic phrenic discharge disappeared during HFV in all animals at normal arterial PCO2 levels. Rhythmic activity returned after neuromuscular blockade in the vagally intact animal. Although vagotomy alone also restored phrenic discharge, this activity was further enhanced by subsequent neuromuscular blockade. Therefore we suggest that apnea during HFV results from inspiratory inhibition mediated by both chest wall and vagal afferent mechanisms.

Animals↗

PubMed1994

Neuromuscular blockade: indications, peripheral nerve stimulation, and other concurrent interventions.

Neuromuscular blocking agents (NMBAs) are used in critical illness to reduce metabolic demands and prevent ventilator asynchrony in patients refractory to sedation and anxiolysis. Concurrent interventions for patients receiving neuromuscular blockade include many factors related to prevention, maintenance, and monitoring during immobilization. Prevention interventions include skin care, turning regimes, physical therapy, eye care, and pulmonary toilet to prevent atelectasis, pneumonia, skin breakdown, and corneal ulceration. Maintenance interventions include provision of nutrition, sedation, anxiolysis, and psychosocial support. Monitoring interventions include trending oxygenation parameters and ventilatory care parameters, as well as assessment of the depth of paralysis by assessing clinical evidence of movement, airway pressure waveforms, and peripheral nerve stimulation results. Cost of therapy is influenced by preventing the side-effects of immobility, the choice of NMBA, and concurrent drug therapies, as well as by titration of the NMBA to the lowest drug dose possible to obtain clinical end-points. Clinical end-points are individualized by the prescribing physician and may range from "no movement" to "movement acceptable but no evidence of spontaneous respirations" to "movement acceptable but no ventilator asynchrony." Whenever "no movement"c is identified as the goal, a nerve stimulator is used to identify the depth of paralysis and prevent accidental surplus drug administration, which may result in prolonged paralysis. Methods for using the nerve stimulator and troubleshooting techniques are discussed.

Critical Care↗

PubMed1990

The effect of bambuterol on plasma cholinesterase activity and suxamethonium-induced neuromuscular blockade in subjects heterozygous for abnormal plasma cholinesterase.

Bambuterol is a new bronchodilator which is also a reversible inhibitor of plasma cholinesterase. In patients with normal plasma cholinesterase genotype, bambuterol prolongs suxamethonium-induced neuromuscular blockade. In the present study, we investigated the interaction of bambuterol and suxamethonium in nine patients heterozygous for abnormal plasma cholinesterase during anaesthesia with fentanyl, thiopentone, halothane and nitrous oxide in oxygen. The patients (seven E1uE1a and two E1uE1s) were given 20 mg of bambuterol orally 2 h before anaesthesia. Suxamethonium 1 mg.kg-1 was given for tracheal intubation. The neuromuscular function was monitored using train-of-four (TOF) stimulation of the ulnar nerve and a force displacement transducer. Plasma cholinesterase activity decreased in all patients following bambuterol (P less than 0.001). In patients with genotype E1uE1a, median time to 90% recovery of twitch height and TOF ratio greater than or equal to 0.7 (37.5 min) was prolonged compared to 28 E1uE1a patients not treated with bambuterol (14.0 min) (P less than 0.001). Four of these patients developed a phase II block apparently not correlated to plasma cholinesterase activity. In the E1uE1s; patients, full recovery was seen after 22.0 and 31.4 min, respectively. It is concluded that in patients heterozygous for abnormal plasma cholinesterase, bambuterol 20 mg taken 2 h before anaesthesia causes a 2-3 times prolongation of the neuromuscular blockade following suxamethonium 1 mg.kg-1 and in some patients a phase II block.

Adult↗

PubMed1995

[Neuromuscular blockade with atracurium in dermatomyositis].

Dermatomyositis (DM) is a rare disease of unknown aetiology involving weakness of proximal muscles, myalgia and impairment of the integument. Due to its low incidence, only few reports exist on the anaesthesiologic management of neuromuscular blockade in patients with DM considered for surgical therapy. In this setting, special attention should be given to the administration of muscle relaxants since an increased sensitivity to these drugs in neuromuscular diseases may be expected. METHODS. This case report describes the neuromuscular monitoring of a female patient aged 53 years with DM undergoing strumectomy and treated with methotrexate and prednylidene. Muscle relaxation was induced with 0.35 mg/kg atracurium (1.5 x ED95). An additional bolus of 0.07 mg/kg was administered 50 min later. Control of sufficient relaxation was performed by tactile methods, and time of onset (TO), duration of action (DA) and recovery index (RI) were measured. RESULTS. Relaxation was obtained within TO of 3 min, DA of 50 min and RI of 11 min. These timer indicate slightly increased sensitivity to atracurium. The postoperative outcome demonstrated no muscular weakness and sufficient spontaneous ventilation. DISCUSSION. To date, few experiences of neuromuscular blockade with atracurium in DM have been presented, hence this report. In addition, no standard recommendations are given regarding the application of nondepolarizing muscle relaxants in this context. In our case, atracurium could be implemented as a safe drug under neuromuscular monitoring.

Atracurium↗

PubMedDate not supplied

Reversion by calcium but not by Bay K 8644 of neuromuscular blockade induced by nicardipine.

We compared the effects of nicardipine on indirectly and directly elicited twitches in phrenic-hemidiaphragm preparations from rats, and the effects of calcium and Bay K 8644 on nicardipine-induced neuromuscular blockade. Nicardipine (5-250 microM) decreased both directly and indirectly elicited muscular contractions in a concentration-dependent way. The inhibitory effect was greater when the preparation was indirectly stimulated. Nicardipine antagonism of indirectly elicited contractions was reversed in an apparently competitive way by calcium (1-4 mM). In contrast, the calcium channel agonist Bay K 8644 (0.1 and 1 microM) had no effects per se, nor did it reverse neuromuscular blockade induced by nicardipine. Interestingly, Bay K 8644, at 10 microM, decreased the height of indirectly elicited muscular contractions. These results suggest that the calcium antagonist nicardipine affects neuromuscular transmission to a greater degree than muscular contraction, this effect being antagonized by calcium. In contrast, the calcium agonist Bay K 8644 was unable to produce any effect as stimulator of calcium channels at the neuromuscular level, indicating that this drug may exhibit tissue specificity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗