<P> "Forty - five seconds after the beginning of the injection, heaviness of the eyelids and transitory diplopia were perceived . At the completion of the injection, diplopia became fixed, but could be noticed only when the subject's eyelids were raised by the operator . As curarization proceeded, it seemed to the subject as if the facial muscles, those of the tongue, pharynx, and lower jaw, the muscles of the neck and back, and the muscles of the extremities became relaxed in about that order . Accompanying the paralysis of the pharynx and the jaw muscles, inability of the subject to swallow was noted...Shortly after the injection was completed the subjects experienced a sensation of increased difficulty in breathing, as if an extra effort was necessary to maintain an adequate respiratory exchange . This sensation was present even though there was no objective evidence of impaired oxygenation or of carbon dioxide retention . It reached its maximum about five minutes after the injection, coinciding with the maximum depression of the vital capacity . In the majority of the experiments the respiratory rate was increased by about 50--100 per cent the first minutes after the injection of any one of the drugs while the tidal volume decreased ." </P> <P> Tubocurarine has a time of onset of around 5 minutes which is relatively slow among neuromuscular - blocking drugs, and has a duration of action of 60 to 120 minutes . It also causes histamine release, now a recognized hallmark of the tetrahydroisioquinolinium class of neuromuscular blocking agents . Histamine release is associated with bronchospasms, hypotension, salivary secretions, making it dangerous for asthmatics, children, and those who are pregnant or lactating . However, the main disadvantage in the use of tubocurarine is its significant ganglion - blocking effect, that manifests as hypotension, in many patients; this constitutes a relative contraindication to its use in patients with myocardial ischaemia . </P> <P> Because of the shortcomings of tubocurare, much research effort was undertaken soon after its clinical introduction to find a suitable replacement . The efforts unleashed a multitude of compounds borne from structure - activity relations developed from the tubocurare molecule . Some key compounds that have seen clinical use are identified in the muscle relaxants template box below . Of the many tried as replacements, only a few enjoyed as much popularity as tubocurarine: pancuronium, vecuronium, rocuronium, atracurium, and cisatracurium . Succinylcholine is a widely used muscle relaxant drug which acts by activating, instead of blocking, the ACh receptor . </P> <P> The potassium channel blocker tetraethylammonium (TEA) has been shown to reverse the effects of tubocurarine . It is thought to do so by increasing ACh release, which counteracts the antagonistic effects of tubocurarine on the ACh receptor . </P>

How does d-tubocurarine act as a muscle relaxant