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Background: Muscarinic receptor antagonists are a usual treatment for chronic airway diseases, with increased bronchoconstriction, like asthma and chronic obstructive pulmonary disease. These diseases are usually accompanied by airway remodeling, involving airway smooth muscle cell (ASMC) proliferation. The purpose of this study was to examine the effect of the muscarinic receptor modulator gallamine on rabbit tracheal ASMC proliferation., Methods: ASMCs were incubated with gallamine (1 nM-10 mM), atropine (1 fM-10 mM), and/or acetylcholine (1 nM-1 mM), in the presence or absence of FBS (1% or 10%). Cell proliferation was estimated by incorporation of radioactive thymidine, the Cell Titer AQueous One Solution method and cell number counting after Trypan blue exclusion. The mechanisms mediating cell proliferation were studied using the PI3K and MAPK inhibitors LY294002 (20 μM) and PD98059 (100 μM), respectively. Cell phenotype was studied by indirect immunofluorescence for α-actin, Myosin Heavy Chain and desmin., Results: ASMC incubation with the muscarinic receptor allosteric modulator gallamine or the muscarinic receptor antagonist atropine increased methyl-[ 3 H]thymidine incorporation and cell number in a dose-dependent manner. ASMC proliferation was mediated via PI3K and MAPK activation and was transient. Gallamine antagonized the mitogenic effect of 1% FBS. Furthermore, gallamine had a similar effect on contractile ASMCs, without synergizing with or affecting acetylcholine induced proliferation, or altering the percentage of ASMCs expressing contractile phenotype marker proteins., Conclusions: Gallamine, in the absence of any agonist, has a transient mitogenic effect on ASMCs, regardless of the cell phenotype, mediated by the PI3K and the MAPK signaling pathways., (Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

The effects of electrical stimulation of the femur, on blood pressure, were examined in anesthetized rats. Two small holes, 3-4 mm apart, were manually drilled into the femur down to the bone marrow. Following this, two stainless-steel electrodes were inserted into the holes, and an electrical square wave current was passed between the electrodes. In central nervous system-intact rats, electrical stimulation of the femur at 5 and 10 mA at 20 Hz for 20 s produced an intensity-dependent decrease in mean arterial blood pressure. This response was abolished by severance of the femoral and sciatic nerves ipsilateral to the stimulation. Furthermore, the renal sympathetic efferent nerve activities (as a representative index of vasoconstrictor activities) decreased following the electrical stimulation of the femur. However, in acutely-spinalized rats (spinalized at the cervical level) the same stimulation increased renal sympathetic efferent nerve activities and mean arterial blood pressure. It was concluded that high-intensity electrical stimulation of the femur reflexively affected blood pressure. It can be inferred that the osteal high-threshold receptors and/or fibers are involved in the afferent nerve pathway, and the efferent nerve pathway is the sympathetic vasoconstrictor nerve. The excitatory response properties at the propriospinal level are modified into an inhibitory response by supraspinal structures., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Muscle relaxing agents are clinically in use for general anaesthesia to optimize the conditions to the endotracheal intubation as well as the surgical conditions. Therefore different musclerelaxants with specific pharmacological characteristics are available. Many factors that depend on the condition of the patient and the used musclerelaxant agent influence the duration of the neuromuscular blockade. Rapid reversal of their effects, particularly in cases of profound blockades, proved to be difficult. In cases of postoperative residual paralysis hypoxic complications because of failure of the ventilation increase the morbidity and mortality of the perioperative period. To avoid these complications in cause of postoperative residual neuromuscular blockade it seems to be necessary to evaluate the status of the muscle function. For the tactile or visual assessment or the objective measurement of stimulation the train-of-four (TOF), double-burst (DBS) or tetanus-stimulation of peripheral nerves like the ulnar nerve may be used. Established methods for the objective monitoring of neuromuscular function is the mechanomyography (MMG), the acceleromyography (AMG), the electromyography (EMG), the kinemyography (KMG) and the phonomyography (PMG). A sufficient recovery of the neuromuscular transmission is reached to a TOF-ratio of 0,9 and should be aimed before the extubation at the end of surgery. No subjective evaluation of the neuromuscular recovery is able to identify residual paralysis above a TOF-ratio of 0,5. Recent studies suggest that objective methods should be used to monitor neuromuscular function to avoid postoperative residual blockades.

Cadmium (Cd) toxicity was produced in male rats to study the role of cholinoceptors in Cd-induced endothelial dysfunction. The changes in the tension of the aortic rings to constrictor and dilator agonists were compared with those of controls. A Cd-induced significant increase in phenylephrine response was associated with a decrease in basal dilator prostanoid release. In Cd-exposed rings, despite an obvious depression in the acetylcholine (ACh) response, the receptor-independent dilation to the calcium ionophore A23187, which elicits a receptor-independent endothelial relaxation, was slightly elevated (p<0.01), but the smooth muscle cell response to the NO donor, sodium nitroprusside (SNP) remained unaltered. Cadmium decreased both the maximal response to ACh (10(-5) M) and its pirenzepine (Prz) sensitive component. The M1 type cholinoceptor-mediated response to ACh decreased in Cd-exposed rings to 10.30 +/- 5.00% from 38.40 +/- 6.90% (p<0.001). Cadmium also reduced the share of indomethacin 1.64% to 13.92 +/- 2.89% (p<0.01), which correlated well with the changes in the M1-mediated response (r=0.991, p<0.0001). Most of the deleterious effect of Cd appears to be restricted to the M1-dependent ACh response. These findings suggest that Cd produces an endothelial dysfunction by impairing the M1 type cholinoceptor mediated response, which seems to be involved in prostanoid release.

We report the case of a patient who was referred for suspected anaphylaxis with anesthetic drugs. Gallamine was diagnosed the responsible drug and our patient developed anaphylaxis during intradermal testing (IDT) with this compound. IDT should be monitored carefully.

The aim of the study was to analyse in a well-established model of neophobia the effects of peripheral and central (ICV) administration of a prototypical and easily penetrating to the brain acetylcholinesterase inhibitor (AChE-I)--physostigmine, hemicholinium, a selective blocker of the high affinity choline uptake sites, as well as muscarinic and nicotinic receptor ligands. Thus, an attempt was made to address the question whether anxiolytic-like effects of AChE-I, reported in the clinic, are directly related to the anti-emotional action. The effects of peripherally and centrally administrated cholinergic ligands on novelty-induced decrease in exploratory behaviour were examined in rats. It was found that in a limited dose-range physostigmine and nicotine given peripherally or ICV selectively disinhibited rat exploration in the open field, whereas scopolamine stimulated animal motor activity and increased thigmotaxis. Locomotor effects of physostigmine and nicotine appeared at the higher doses and could be easily separated from their anti-neophobic action. The rat's exploratory behaviour tended to be attenuated by central administration of hemicholinium (a choline uptake blocker), and it was significantly inhibited by mecamylamine (a nicotinic receptor antagonist), and pirenzepine (a selective M1 receptor antagonist). Gallamine, a selective M2 receptor antagonist, did not influence on animal novelty-induced anxiety-related behaviour. It is concluded that AChE-I can selectively affect brain emotional processes evoked by neophobia-related stimuli. Probably both nicotinic and M1 cholinergic receptors mediate such an action of AChE-I.

Objective: To assess the relative efficacy of a pacing esophageal stethoscope and intermittent boluses (40 mg) of gallamine in correcting sinus bradycardia (SB) during coronary artery surgery., Design: The study was prospective, randomized, and controlled., Setting: A community hospital., Participants: Fifty patients scheduled for elective coronary artery surgery., Interventions: The patients were randomly allocated to receive treatment for an SB (less than 60 BPM) with either transesophageal atrial pacing (TAP) or gallamine., Measurements and Main Results: Heart rate, blood pressure, and systemic hemodynamics were measured. The electrocardiogram was monitored for rate, rhythm, and conduction abnormalities. Twenty-four of the 25 TAP patients could be paced at a rate of 70 BPM after SB. Cardiac index increased from 1.90 to 2.56 L/min/m2. In the gallamine group, heart rate was increased from 50 to 66 BPM, but cardiac index only increased to 2.2 L/min/m2, and 2 patients developed nodal rhythms. Eight of these patients had peak heart rates over 80 BPM, and two were over 90 BPM., Conclusions: The ability to reliably and precisely control heart rate was superior with TAP compared with intermittent bolus dosing with gallamine.

1. Using a guinea-pig model of allergic asthma, in which the animals display early (0-5 h) and late phase (8-23 h after antigen challenge) bronchoconstrictor reactions, the function of prejunctional inhibitory M2 and postjunctional M3 receptors in isolated tracheal preparations have been investigated. In addition, cardiac M2 receptor function in vitro and bronchial responsiveness to histamine in vivo were evaluated. 2. Sensitivity to inhaled histamine was increased 3.1 fold and 1.6 fold after the early and late allergic reactions (i.e. at 5 h and 23 h after a single ovalbumin challenge), respectively. At 23 h after the last of four allergen challenges, executed on four consecutive days, bronchial hyperresponsiveness to histamine was diminished to 1.3 fold. 3. After the early response, there was no change in cardiac muscarinic M2 receptor function, since in left atria pD2 (-log EC50) and Emax values of pilocarpine and pKB values of AQ-RA 741, a selective M2 receptor antagonist, were not significantly different from controls (unchallenged sensitized animals), and this also applied to methacholine pD2 values for muscarinic M3 receptors in tracheal smooth muscle. 4. Prejunctional inhibitory muscarinic M2 autoreceptors in airway smooth muscle were markedly dysfunctional after the early allergic response, since potentiation of electrically evoked twitch contractions of tracheal preparations by low concentrations of the M2-selective muscarinic receptor antagonists, gallamine, methoctramine, AQ-RA 741 and AF-DX 116, which is the result of M2 receptor blockade, was clearly and significantly diminished compared to controls. However, after the late response, both in single and repeatedly challenged animals, twitch potentiation was not significantly different from and similar to controls, indicating restoration of M2 receptor function during the late allergic reaction.5. It is concluded that dysfunction of muscarinic M2 autoreceptors in the airways of sensitized and challenged guinea-pigs is already present after the early allergic reaction, and that it has recovered after the late response. Since histamine-induced bronchoconstriction involves vagal pathways, the present results suggest that bronchial hyperresponsiveness to histamine is partly due to M2 auto receptor dysfunction, leading to increased release of acetylcholine.

Binding and autoradiographic studies have shown the presence of a rather high density of M2 muscarinic subtype receptors and the apparent absence or low density of the M1 subtype in the septum. We tested the hypothesis that, in the urethane-anesthetized rat, septal M2 receptors are involved in the generation of the hippocampal theta (theta) rhythm induced by intraseptal administration of carbachol, a potent cholinomimetic agent. Carbachol-induced theta was blocked by local infusion of the unspecific muscarinic antagonist agent, atropine (20 micrograms (29.55 nM)), given 10 min prior to carbachol. The intraseptal administration of low to high doses of gallamine (range: 20-180 micrograms (22.43-201.90 nM)), a specific M2 antagonist which displays high affinity for the septal region, resulted in significant changes in the electrophysiological characteristics of carbachol-induced theta but failed to abolish this rhythm. It is suggested that the latter may have resulted from a combined activation of both M2 and non-M2 receptors at septal level.

An African electric fish, Gymnarchus, and a South American electric fish, Eigenmannia, are believed to have evolved their electrosensory systems independently. Both fishes, nevertheless, gradually shift the frequency of electric organ discharge away when they encounter a neighbor of a similar discharge frequency. Computational algorithms employed by Gymnarchus for this jamming avoidance response have been identified in this study for comparison with those of extensively studied Eigenmannia. 1. Gymnarchus determines whether it should raise or lower its discharge frequency based solely upon the signal mixture of its own reafferent and the exafferent signal from a neighbor, and does not internally refer to the pacemaker command signal which drives its own discharge. 2. The signal mixture is analyzed in terms of the time courses of amplitude modulation and phase modulation at each area of the body surface. 3. Phase of the signal mixture at each area is compared with that of another area for the detection of phase modulation. 4. Unambiguous information necessary for the jamming avoidance response is extracted by integrating information from all body areas each of which yields ambiguous information. 5. These computational features are identical to those of Eigenmannia, suggesting that the neural circuit for jamming avoidance responses may have evolved from preexisting mechanisms for electrolocation in both fishes.

Multiple intrahippocampal injections of gallamine impair performance of a representational memory task in rats. The binding of [3H]-(-)-quinuclidinyl benzilate (QNB) to rat brain sections was measured to determine if changes in receptor binding were associated with the deleterious effects of gallamine. [3H]-(-)-QNB binding to sections taken from gallamine-injected animals was compared with binding in saline-injected control animals. Autoradiographic analyses indicated an increase in [3H]-(-)-QNB binding sites within all layers of the cerebral cortex and in the superior colliculus in gallamine-treated animals as compared to saline-injected controls. Significant increases were noted in cortical layers IV and V (P less than 0.025) in gallamine-treated animals. No significant changes (P greater than 0.05) in the number of binding sites were observed in the hippocampus, neostriatum or various thalamic nuclei. The ability of unlabeled pirenzepine, gallamine and carbamylcholine to inhibit 0.2 nM [3H]-(-)-QNB binding also was measured to determine changes in the distribution of receptor subtypes. No significant changes were observed in any brain region for the binding of the selective antagonists pirenzepine and gallamine or the agonist carbamyl-choline. Although other possibilities are considered, the data suggest that an increase in the number of muscarinic receptors may contribute to the observed behavioral deficits associated with long-term gallamine treatment.

A prospective clinical comparison of d-tubocurarine, alcuronium, gallamine and pancuronium was performed in 400 surgical patients. Various parameters usually followed during clinical anaesthesia were recorded from the beginning of, to the recovery from anaesthesia. Endotracheal intubation was performed with or without suxamethonium. Intubation was always possible in 1-3 min when different muscle relaxants were used in the following initial doses: d-tubocurarine 0.4 mg/kg, alcuronium 0.3 mg/kg, gallamine 1.8 mg/kg, and suxamethonium 0.8 mg/kg. However, there was a statistically significant inferiority of the d-tubocurarine and gallamine groups. The use of suxamethonium seemed to shorten the duration of the initial dose of the nondepolarising agents and also to increase especially the dose of gallamine when calculated as mg/kg/h. It should be mentioned that the non-depolarising agents were given soon after suxamethonium without waiting for the return of spontaneous respiration. Pancuronium and alcuronium caused least changes in the cardiovascular parameters. Erythematous skin reactions were seen mostly after the use of d-tubocurarine and suxamethonium. This could depend on histamine liberating potency of these muscle relaxants.

Neuromuscular blockade studies often use the thumb adductor twitch response to ulna nerve stimulation. Two factors that may influence the results are the resting muscle tension (initial fiber length) and the pattern of the stimulus wave form. This study was undertaken to improve understanding of the effect of these factors and lead to better controlled study conditions and more consistent data. During nitrous oxide-barbiturate-narcotic anesthesia in 10 normal adult patients, as the resting thumb tension was increased from 50 to 200 g, the evoked thumb adductor twitch response (Grass stimulator, 0.25 Hz) was augmented by 28%. There was only a 2.5% increase in the evoked (developed) tension when the resting tension was further increased from 200 to 300 g. Developed tension at 50 g was significantly (p less than 0.001) less than at the other resting tensions. The developed tension at 100 g was also significantly (p less than 0.05) less than at resting tensions of 200 or 300 g. Cumulative dose-response curves for gallamine in nine patients were not significantly altered by increasing resting tension from 50 to 200 g. Biphasic (Block-Aide monitor) or single square wave (Grass stimulator) stimuli wave forms in nine normal adult patients yielded gallamine dose-response curves that were not statistically different. The muscle response to biphasic stimulation during a non-depolarizing blockade was not affected by the average muscle refractory period. Because of the significantly lower developed tension at resting tension settings of 50 to 100 g, a practical consideration during neuromuscular function studies would be to have the resting thumb tension adjusted and rechecked for each patient and kept within the 200-300-g range to ensure maximum uniform developed tension. The type of stimulus wave form selected will not affect results as long as it is used consistently throughout the study.

Eighty per cent paralysis was induced and maintained for 90 minute in the sheep by computer-controlled injection of gallamine, pancuronium, alcuronium or d-tubocurarine, using the integrated electromyogram as a measure of neuromuscular transmission. The dosage pattern consisted of a loading phase before any IEMG depression was detected, an onset phase during which a moderate amount of drug was required to achieve increasing paralysis, and a maintenance phase during which a substantially constant and relatively low infusion rate was required. The steady state rates of infusion in microgram/kg/min during "maintenance" was found to be 6.0 for gallamine, 0.15 for pancuronium, 0.2 for alcuronium and 0.5 for d-tubocurarine.

Gallamine, metocurine, pancuronium, and d-tubocurarine were compared when given alone and in combination with isolated guinea pig nerve-lumbrical preparations stimulated via the nerve. The experimental design was set up to control the effects of variation among preparations, order of administration, and time of administration (i.e., fresh vs. older preparation). The result was an assay able to measure potentiation with a coefficient of variation of 3%. A format for a graphic presentation to summarize such results is presented and discussed. Two combinations, gallamine plus d-tubocurarine and gallamine plus pancuronium, showed no sign of an interaction beyond that to be expected from a simple competitive interaction. Two others, metocurine plus pancuronium and gallamine plus metocurine, showed about a twofold greater potency when combined than would have been expected. The last two sets, pancuronium plus d-tubocurarine and metocurine plus d-tubocurarine, showed a slight degree of potentiation. These studies demonstrate that the deviation from simple additivity seen in vivo persists when examined in a system free from artifacts associated with uptake and distribution in the whole organism.

Preoperative administration of gallamine was evaluated during inhalation anaesthesia with nitrous-oxide and halothane with two administrations of suxamethonium 1 mg/kg body weight, 5 min apart. Sixty healthy patients were randomly divided into three groups and preanaesthetic gallamine, 0.3, 0.4 or 0.5 mg/kg body weight, respectively was administered intravenously 3 min before induction, according to the allocation. Just before induction of anaesthesia the patients were examined for signs and symptoms of partial curarization. After induction of anaesthesia by nitrous-oxide-oxygen-halothane, suxamethonium 1 mg/kg was given intravenously. Exactly 5 min later the same dose was repeated. ECG was monitored continuously and serum potassium, Pao2 and Paco2 were measured at appropriate intervals. It was found that none of the examined doses of gallamine gave any reliable protection against serious bradyarrhythmias after repeated doses of suxamethonium. Furthermore the higher doses of gallamine caused an unacceptably high frequency of patients with tachycardia and signs and symptoms of partial curarization.

The administration of minute doses of all currently available nondepolarizing muscle relaxants result in an increase in contractile force of the skeletal muscles. This surprising finding has been obtained by means of mechanograms of the hand muscles after electrical stimulation of the ulnar nerve (100-200 volts, 0.3 msec, 0.2 Hz). Higher doses produce a decrease in contractile force and a paralysis of the skiltalmuscles. The paradoxical action of muscle relaxants can be explained by repetitive firing of the muscle action potential as has been demonstrated in the phrenic nerve-diaphragm preparation with tubocurarine and gallamine.

Plasma concentrations of gallamine were determined in 6 patients undergoing anaesthesia for elective surgery receiving a single intravenous bolus dose of 2 mg/kg and in a further 11 patients requiring additional doses (0.5 to 2 mg/kg) of the relaxant. The two-compartment open model was found to characterize adequately both the single and multiple dose data. No significant differences were noted when the model-independent pharmacokinetic parameters between the two groups of patients were compared with the exception of the distribution phase half-life (t1/2 alpha) (6.70 min single vs 9.19 min multiple p less than 0.05). Mean values for the pooled data for the half-life (t1/2 beta), plasma clearance (Clp) and volume of distribution (Vd beta) were 134.58 min, 1.20 ml/min/kg and 225.28 ml/kg respectively. Evoked twitch response was monitored in each patient to assess the degree of neuromuscular blockade. In only one patient was the bolus dose sufficient to produce complete (100%) blockade, thus the degree of maximal response varied between 78 to 100% and took some 3 to 10 minutes after dose administration. The concurrently measured gallamine plasma concentrations ranged from 9.30 to 19.20 micrograms/ml. Linear regression of the offset data (20 to 80% paralysis) in 10 patients revealed a recovery rate of 0.35 to 1.33%/min. For 5 patients where offset data was available over the entire range of response (0 to 100%) the calculated mean effective plasma concentrations for gallamine at 50 and 95% paralysis (ECp50, ECp95) were found to vary between 3.43 to 10.28 micrograms/ml, and 5.66 to 23.37 micrograms/ml respectively.

Fifty patients were pretreated with either suxamethonium 10 mg or gallamine 20 mg before an injection of suxamethonium 1 mg kg-1. The effect of the pretreatment upon neuromuscular transmission was monitored by recording the mechanical response of the adductor pollicis muscle to indirect stimulation, using a 2-Hz train-of-four stimulus repeated every 12 s. The pretreatment injection of suxamethonium caused fasciculation in one-quarter of the patients studied. Significant neuromuscular blockade occurred during pretreatment in 16 of the 25 patients investigated. Pretreatment with gallamine 20 mg predictably decreased the efficacy of the intubating injection of suxamethonium, making intubation more difficult. The frequency of muscle pain was similar in both groups.

Sixty coldwater and warmwater fish ranging in weight from 2 to 35 kg were injected intramuscularly with the hypnotics alphaxalone-alphadolone and metomidate hydrochloride and the non-depolarising muscle relaxant gallamine triethiodide using a laser-aimed underwater dart gun. Alphaxalone-alphadolone produced sufficient sedation for easy netting within five to 20 minutes at doses between 0.3 and 0.5 ml/kg, with induction being somewhat faster in warmwater species. The pattern of induction was similar with metomidate but required doses of 40 to 60 mg/kg. The muscle relaxant gallamine triethiodide showed promise as a practical agent for the capture and handling of large fish by virtue of its smooth induction of paralysis at doses between 1 and 3 mg/kg and its reversible supplementation with orally administered metomidate hydrochloride.

Kinetics of gallamine, a neuromuscular blocker, were investigated in 22 adult patients undergoing surgery involving cardiopulmonary bypass (CPB). Approximately 60 min before CPB, 11 patients received 480 mg gallamine IV; the other 11 patients received an initial dose of 240 mg IV, followed by another 240 mg through the pump priming fluid at the start of CPB. In 14 of our patients, the time course of gallamine concentrations in the plasma before, during, and after CPB was similar to that in normal surgical patients, indicating little or no effect of cardiac disease or CPB. In the remaining patients, perturbations were not observed before CPB, but with its onset there were varying changes, typically, rises in gallamine concentration ranging from an alteration during the period of CPB only or during the elimination phase, to an alteration at all times after starting CPB. Although the mechanism for this rise in gallamine plasma concentrations during and after CPB is not known, computer simulations suggest that it is due to a contraction in blood volume or decreased tissue perfusion during the period of extracorporeal circulation. Gallamine disposition differed only moderately in our patients from that in control patients. Therefore, from a kinetic viewpoint, provided that renal function is not impaired, gallamine is not contraindicated in CPB surgery.

Fourteen patients undergoing elective surgery were studied at two levels of gallamine dosage. Seven patients received a single bolus dose of 4 mg/kg, and the remainder received 6 mg/kg. The venous plasma concentration-time data from both groups were characterized in terms of a two-compartment open model. No significant differences in the various pharmacokinetic parameters were noted. However the distribution and clearance terms from these two patient groups were significantly higher than those obtained with a previous group of patients receiving lower (2 mg/kg) single and multiple doses. Assessment of neuromuscular twitch response showed that maximum blockade was attained in all patients within 5 min with the time to peak effect being dose dependent. Recovery from paralysis as assessed at 99, 95 and 90% paralysis indicated that the duration of action was similarly dose dependent. The concurrently measured plasma concentrations showed wide variation but were higher at more profound levels of paralysis. Arterial blood samples for 5 patients receiving the 4 mg/kg gallamine dose were taken simultaneously with the venous samples over the first sixty minutes. No significant arterio-venous differences in gallamine plasma concentration were noted at any time interval in all subjects.

Supramaximal paired stimuli were applied to the ulnar nerve, and the amplitude of the muscle action potential evoked in the abductor digiti minimi by the second member of the stimulus pair (test response) was compared with that evoked by the first component (conditioning response). The interval between the two components of the stimulus pair (the pair interval) was increased stepwise from 7 to 100 msec and a curve (recovery curve) was obtained by relating the changes in pair interval to the difference in amplitude of the test and conditioning responses. Alterations of the recovery curve (RC) during partial paralysis by muscle relaxants were investigated in healthy adult patients under the lightest plane of general anaesthesia. The control curve obtained in 32 subjects before the administration of a muscle relaxant drug was characterized by slight depressions at very short intervals of paired stimuli, followed by a slight potentiation at 20-100 msec. With non-depolarizing relaxants, RC altered to the characteristic pattern of potentiation at very short intervals of stimuli, followed by a notable depression at longer intervals. In depolarizing blocks with small doses of suxamethonium, the depression of RC at short intervals in the control was enhanced and the pattern of RC was different from that of non-depolarizing agents. When desensitization blocks were instigated by the i.v. administration of suxamethonium, the RC patterns were similar to those of competitive agents.

'Lissive anaesthesia', the administration of a small dose of a non-depolarising muscle relaxant to a patient breathing nitrous oxide, oxygen and an anaesthetic vapour, is a technique popularly employed for minor procedures. In this study, the effects of intravenous gallamine triethiodide (40 mg) on the blood-gas status of 20 patients under general anaesthesia with oxygen, nitrous oxide and halothane after pethidine and atropine premedication, were assessed. The results are compared with those obtained from a control group of 10 patients anaesthetised in an identical manner, but omitting the muscle relaxant drug. All patients in both the relaxant and control groups in this study developed respiratory acidaemia. The rise in mean arterial carbon dioxide tension was, however, greater after injection of gallamine. Significant hypoxia or metabolic acidaemia was not encountered, except in one grossly obese patient in the gallamine group. The implications of these findings are discussed.

A technique combining an intravenous bolus and intravenous infusion regimen of gallamine based on its pharmacokinetics was developed to produce continuous relaxation during surgery. The combination of a bolus dose of gallamine, 2.5 mg/kg, and infusion, 0.8 mg/kg/hr, was tested in 11 patients. In 10 patients, surgery continued long enough to allow demonstration of an apparent plateau in the serum gallamine concentrations. At the cessation of the infusion, the mean gallamine concentration of 11.8 microgram/ml was associated with an average paralysis intensity of 92%. Pharmacokinetic analysis of the gallamine serum concentration-time data was fitted to a three-compartment model. In this study of 50- to 76-year-old patients, the most striking difference from other studies was that the elimination halflife averaged 247 minutes in this study whereas 128 to 141 minutes has been reported previously.