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Gallamine triethiodide selectively blocks voltage-gated potassium channels in Ranvier nodes.

The effects of gallamine on ionic currents in single intact Ranvier nodes of the toad Xenopus were investigated. The following fully reversible effects were observed: 1. With a test concentration of 1 mmol/l the current-voltage relation of steady-state potassium currents, IK ss exhibited a complete block of IK ss up to about V = 110 mV; with stronger depolarisations the block was incomplete. The peak sodium currents, in contrast, were not affected. 2. At the same test concentration the potassium permeability constant PK was reduced by 92% from its normal value, while the sodium permeability constant PNa decreased by only 8%. 3. Concentration-response relations of the block of PK yielded an apparent dissociation constant of 30 micromol/l and a steepness parameter of unity. Patch-clamp experiments on cloned Kv1.1, Kv1.2, Kv1.3 and Kv3.1 channels yielded apparent dissociation constants of 86, 19, >>100 and 121 micromol/l, respectively. Our findings show that gallamine is particularly well suited for separating potassium and sodium currents in axonal current ensembles. They also strongly suggest that potassium currents in Ranvier nodes of Xenopus are mainly carried by an ensemble of Kv1.1 and 1.2 channels.

Animals↗

Anaphylaxis to precurarising doses of gallamine triethiodide.

Two cases are described in which patients developed acute anaphylactic reactions to precurarising doses of gallamine. Life threatening complications can arise from the use of small doses of drugs as adjuncts to anaesthesia and raises the question whether the benefits of precurarisation outweigh the risks of anaphylaxis.

Adult↗

An anaphylactoid reaction to gallamine triethiodide.

A patient suffered profound anaphylactoid reaction during anaesthesia. Intradermal skin testing confirmed the clinical impression that gallamine caused the reaction. The method of testing is discussed. Previous reports of hypersensitivity to the drug are reviewed, and the use of adrenaline, antihistamines and corticosteroids in patient management are considered.

Adult↗

Cathodic adsorptive stripping voltammetric determination of muscle relaxant: gallamine triethiodide (flaxedil).

A sensitive and simple voltammetric method of analysis is developed for the determination of trace amounts of gallamine triethiode in phosphate media. This method is based on controlled adsorptive preconcentration of the relaxant onto a Hanging Mercury Drop Electrode (HMDE) whereby mercurous iodide salt(s) are formed. The technique used is Cathodic Linear Sweep Stripping Voltammetry (CLSSV). The adsorptive response was evaluated with respect to preconcentration time and potential. As little as 3 x 10(-9) mol dm(-3) i.e. 2.7 ppb flaxedil (proconcentration time 300 seconds) can be determined successfully. The application of this method was tested in the determination of flaxedil in pharmaceutical preparation (ampoules).

Chemistry Techniques, Analytical↗

Pharmacokinetic studies in man with gallamine triethiodide. II. Single 4 and 6 mg/kg i.v. doses.

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.

Adolescent↗