“…However n can be increased to 6 without affecting potency [117]. This contrasts to the preferred n > 6 carbon spacer in the bisammonio alkane series related to W84 (7). The properties of asymmetrical analogs of the bispyridinium oximes and the (2,6-dichlorobenzyl)ether derivatives (R ≠ R') will be considered in later sections.…”
Section: Molecules Related To Neuromuscular Blockers -Bisonium Ligandsmentioning
confidence: 93%
“…This was the first definition of receptor subtypes even though Dale, at that time, was not familiar with the receptor concept. It took the brilliant work of Loewi and Navratil [6] and Feldberg and Krayer [7] to establish the chemical basis of neurotransmission and identify ACh as the endogenous neurotransmitter at nicotinic and muscarinic receptors.…”
Section: First Indications Of Allosterism At Muscarinic Receptorsmentioning
The evaluation of allosteric ligands at muscarinic receptors is discussed in terms of the ability of the experimental data to be interpreted by the allosteric ternary complex model. The compilation of useful SAR information of allosteric ligands is not simple, especially for muscarinic receptors, where there are multiple allosteric sites and complex interactions.
“…However n can be increased to 6 without affecting potency [117]. This contrasts to the preferred n > 6 carbon spacer in the bisammonio alkane series related to W84 (7). The properties of asymmetrical analogs of the bispyridinium oximes and the (2,6-dichlorobenzyl)ether derivatives (R ≠ R') will be considered in later sections.…”
Section: Molecules Related To Neuromuscular Blockers -Bisonium Ligandsmentioning
confidence: 93%
“…This was the first definition of receptor subtypes even though Dale, at that time, was not familiar with the receptor concept. It took the brilliant work of Loewi and Navratil [6] and Feldberg and Krayer [7] to establish the chemical basis of neurotransmission and identify ACh as the endogenous neurotransmitter at nicotinic and muscarinic receptors.…”
Section: First Indications Of Allosterism At Muscarinic Receptorsmentioning
The evaluation of allosteric ligands at muscarinic receptors is discussed in terms of the ability of the experimental data to be interpreted by the allosteric ternary complex model. The compilation of useful SAR information of allosteric ligands is not simple, especially for muscarinic receptors, where there are multiple allosteric sites and complex interactions.
“…Loewi termed this hypothetical chemical substance 'Vagustoff' and later identified it as acetylcholine. Release of a similar substance in the mammalian heart was demonstrated by Feldberg & Krayer (1933). Dale, Feldberg & V gt (1936) later reported the release of acetylcholine at the neuromuscular junction following stimulation of motor nerves to skeletal muscle.…”
“…6 Loewi’s discovery was eventually confirmed in warm
blooded animals with more highly organized nervous systems as Rylant in 1927
extended Loewi’s frog experiments to rabbits 7 and Feldberg and Krayer in 1933 to cats and
dogs. 8 …”
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