Effects of Analogues of Choline on Neuromuscular Transmission

Bowman, W. C.; Hemsworth, B. A.; Rand, M. J.

doi:10.1111/j.1749-6632.1967.tb53788.x

Cited by 42 publications

(29 citation statements)

References 35 publications

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“…A choline-reversible transmission failure produced selectively in a rapidly stimulated nerve-muscle preparation is an indication of a pre-junctional inhibitory action on acetylcholine synthesis (Reitzel & Long, 1959;Bowman, Hemsworth & Rand, 1967), and all the compounds were tested for this effect.…”

Section: Responises Of Rapidly Stimulated Preparationsmentioning

confidence: 99%

The neuromuscular blocking action of a series of bicyclic bis‐onium esters

Marshall

1968

British J Pharmacology

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, C.J 1. Thirteen bicyclic dicholine esters have been tested on mammalian and avian skeletal muscle preparations. 2. One of the compounds exhibited depolarizing activity in all the preparations. 3. Three of the compounds exhibited depolarizing or dual-blocking activity in avian and denervated mammalian preparations, but exhibited non-depolarizing blocking activity in innervated mammalian preparations. 4. The remaining compounds exhibited non-depolarizing blocking activity with evidence of an additional facilitatory action. 5. The activity exhibited was dependent upon the onium substituents and the structure of the bicycic ring. 6. All the compounds exhibited a choline-reversible block in the rapidly stimulated rat diaphragm preparation and six of them exhibited a secondary choline-reversible block of the rapidly stimulated cat tibialis anterior muscle.Several dicholine esters of a, w dicarboxylic acids containing cyclic structures have been synthesized and tested with the aim of producing a potent short-acting muscle relaxant without the depolarizing activity of suxamethonium (for reviews, see Bovet, 1951Bovet, , 1959Brucke, 1956 Koch & Kotlan (1965). The formulae of the compounds are shown in Table 1. MethodsThe compounds were tested on the following preparations.(a) The tibialis anterior muscles of cats anaesthetized with chloralose (80 mg/kg, injected intraperitoneally). Maximal twitches of a tibialis anterior muscle were elicited once every 10 sec by rectangular pulses (50 lisec duration) applied to the sciatic nerve. The strength of the shocks was about twice that required to evoke a maximal twitch. In some experiments maximal twitches of both tibialis anterior

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Section: Responises Of Rapidly Stimulated Preparationsmentioning

confidence: 99%

The neuromuscular blocking action of a series of bicyclic bis‐onium esters

Marshall

1968

British J Pharmacology

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“…The former blocks by a postjunctional non-depolarizing mechanism whereas the latter's effects are largely prejunctional (Bowman & Rand, 1961). Rand (1962) andBowman et al (1967) reported postjunctional neuromuscular blocking effects in several choline analogues in which groups larger than ethyl were substituted on the nitrogen atom.…”

Section: Discussionmentioning

confidence: 99%

“…The rate of stimulation has little effect on the depth and duration of block caused by depolarizing agents. Non-depolarizing agents, however, are much more effective in rapidly stimulated muscles, whereas choline analogues with prejunctional activity alone are able to cause a depression of the twitch only when rapid rates of stimulation are used (Bowman et al, 1967).…”

Section: Mechanism Of Neuromuscular Blockadementioning

confidence: 99%

“…The neuromuscular blocking action of several ester compounds depends largely on the nature of the choline moiety (Marshall, 1968;Dowd, Jennings, Marshall & Tracy, 1968). The pharmacology of triethylcholine and other analogues of choline has been studied by Bowman & Rand (1961, 1962 and Bowman, Hemsworth & Rand (1967). Choline and its analogues produce neuromuscular blockade by depolarizing, non-depolarizing, and prejunctional mechanisms, the action of each substance depending on the nature of the groups substituted on the nitrogen atom (Hutter, 1952;Bowman & Rand, 1961, 1962Bowman et al, 1967).…”

Section: Mechanism Of Neuromuscular Blockadementioning

confidence: 99%

“…The pharmacology of triethylcholine and other analogues of choline has been studied by Bowman & Rand (1961, 1962 and Bowman, Hemsworth & Rand (1967). Choline and its analogues produce neuromuscular blockade by depolarizing, non-depolarizing, and prejunctional mechanisms, the action of each substance depending on the nature of the groups substituted on the nitrogen atom (Hutter, 1952;Bowman & Rand, 1961, 1962Bowman et al, 1967). The rate of stimulation has little effect on the depth and duration of block caused by depolarizing agents.…”

Section: Mechanism Of Neuromuscular Blockadementioning

confidence: 99%

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Neuromuscular blocking activity of a new series of quaternary N‐substituted choline esters

Ginsburg

Kitz²,

Savarese³

1971

British J Pharmacology

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Summary1. The neuromuscular blocking activity of a new group of mono-and diquaternary N-substituted choline esters of several carboxylic acids has been evaluated in various whole animal preparations in the mouse, rat and cat. 2. A basic non-depolarizing mechanism was present in all but one compound -a depolarizing agent, which was studied for comparison. There was evidence of facilitatory activity and nicotinic stimulation in the monoquaternary compounds. These effects were diminished in the diquaternary compounds.3. The presence of a bulky aromatic ring system on the nitrogen atom appeared to increase both neuromuscular blocking potency and facilitatory activity in the experimental animal. A similar relationship had previously been demonstrated in vitro in another study. 4. The duration of action, although short in most compounds, did not correlate well with previously determined in vitro hydrolysis rates, possibly because of species differences. 5. The general pharmacology of each compound appeared to depend considerably upon the structure of the choline moiety.

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Antagonism of Neuromuscular Actions of Hexamethonium by Choline Precursors

Chiou

1974

Journal of Pharmaceutical Sciences

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Effects of Analogues of Choline on Neuromuscular Transmission

Cited by 42 publications

References 35 publications

The neuromuscular blocking action of a series of bicyclic bis‐onium esters

The neuromuscular blocking action of a series of bicyclic bis‐onium esters

Neuromuscular blocking activity of a new series of quaternary N‐substituted choline esters

Antagonism of Neuromuscular Actions of Hexamethonium by Choline Precursors

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