Rate of onset and offset of neuromuscular block in the isolated rat diaphragm

Brookes, Naomi; Mackay, D.

doi:10.1111/j.1476-5381.1971.tb08034.x

Cited by 4 publications

(5 citation statements)

References 8 publications

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“…If this is so there could be no anti-curare action of hexamethonium like that suggested by Stephenson & Ginsborg (1969). However, it may be that the time constant of receptor clearance calculated from our results does not measure the rate of dissociation of the antagonist-receptor complex; indeed, Brooks & MacKay (1971a) have suggested that the recovery time is determined by the rate of diffusion of the drug from the synapse. The twitch amplitude-occupancy curves suggest that if a just-adequate concentration of antagonist were used to achieve complete block of transmission, after washing out the antagonist from the bath the concentration in the biophase would fall to between one-half and one-quarter of the initial concentration at the halfrecovery time.…”

Section: Discussionmentioning

confidence: 60%

An anti‐curare effect of hexamethonium at the mammalian neuromuscular junction

Ferry

Marshall

1973

British J Pharmacology

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Summary1. Experiments were performed on the isolated phrenic nerve and diaphragm preparation of the rat. 2. In preparations partly blocked with (+ )-tubocurarine, the twitch amplitude increased after hexamethonium. This enhancement was not seen in preparations partly blocked with Mg++ or with gallamine. High concentrations of hexamethonium produced failure of contraction. 3. Extracellular endplate potentials were recorded from blocked preparations. The administration of hexamethonium resulted in an increased amplitude of these potentials only in curarized muscle. 4. Hexamethonium had no anticholinesterase activity nor did it depolarize muscle cells or increase the quantal release of transmitter. 5. It is concluded that hexamethonium exerts a specific anti-curare action. Experiments on the recovery of the twitch after washing out antagonists indicate that this process is limited by diffusion. The difference in rates of diffusion of hexamethonium and (+)-tubocurarine does not account for their interaction. The basis of the anti-curare action of hexamethonium is discussed.

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Section: Discussionmentioning

confidence: 60%

An anti‐curare effect of hexamethonium at the mammalian neuromuscular junction

Ferry

Marshall

1973

British J Pharmacology

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“…One group had been stimulated at four shocks min-' in Krebs solution at 360 C for a period of 4 h during which time the rate of action of gallamine was observed. In the second group of diaphragms which had been stimulated for 5-3-6-3 h, the rate of action of tubocurarine had been studied (Brookes & Mackay, 1971). The mean tortuosity factors found for these groups were 2-73 +014 (S.E.…”

Section: Diffusion Measurementmentioning

confidence: 99%

“…Estimates have also been made of the diffusion coefficients of gallamine and tubocurarine cations, for the work to be described in a later paper (Brookes & Mackay, 1971). The values of D obtained …”

Section: Diffusion Measurementmentioning

confidence: 99%

“…Diffusion coefficients in free solution Values were required for the diffusion coefficients D (in water at 360 C) of sucrose, iodide anion and decamethonium cation. Estimates have also been made of the diffusion coefficients of gallamine and tubocurarine cations, for the work to be described in a later paper (Brookes & Mackay, 1971). The values of D obtained and the origin of each value are shown in Table 1.…”

mentioning

confidence: 99%

“…In order to study the dynamics of neuromuscular blockade in the isolated rat diaphragm (Brookes & Mackay, 1971) it was necessary to determine parameters for diffusion through the muscle interspaces. This has been done by a method similar in principle to that used by Page & Bernstein (1964) for the measurement of diffusion through cat heart muscle.…”

Section: Introductionmentioning

confidence: 99%

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