{'fraction_non_alphanumeric': 0.027777777777777776, 'fraction_numerical': 0.015366430260047281, 'mean_word_length': 5.854251012145749, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Pharmacological analysis of agonist‐antagonist interactions at acetylcholine muscarinic receptors in a new urinary bladder assay

1 Agonist‐antagonist interactions at acetylcholine (ACh) muscarinic receptors have been analysed by use of an improved urinary bladder assay, isolated and intact, from the mouse. With 5‐methylfurmethide as agonist, validated cumulative concentration‐effect curves were obtained in less than 7 min by re‐dosing before the response plateaux began to fade. 2 The pKB value estimated for pirenzepine was 6.76. The pKB values estimated for atropine and N‐methylatropine from data obtained at concentrations which produced dose‐ratios greater than 20 and 60 were 8.90 and 9.58, respectively. 3 The deviation from simple competitive behaviour at low dose‐ratios with atropine and N‐methylatropine was consistent with the operation of saturable antagonist removal processes. The deviation observed with atropine was corrected by pre‐incubation with methylbutyrate, an alternative substrate for ‘atropine esterase’. 4 The simple competitive behaviour of N‐methylatropine was restored following pre‐incubation with the neuronal choline uptake blocker hemicholinium‐3 (HC‐3). However, the pKB estimated for N‐methylatropine under these conditions was low. This latter result could be accounted for by the observed behaviour of HC‐3 as a competitive antagonist of ACh muscarinic receptors (pKB = 4.01). 5 We conclude that the modified mouse urinary bladder assay is suitable for the quantitative analysis of muscarinic receptor interactions. In addition, we postulate the existence of a previously undescribed uptake mechanism for quaternary muscarinic receptor antagonists.