Substrate Report for: Acetylbetamethylcholine

The present electrophysiological study shows that methacholine (MCh), generally regarded as a muscarinic agonist, stimulates the carotid chemoreceptors in pentobarbitone anaesthetized cats. The response consisted of a primary increase in discharge, attributable to nicotinic actions of MCh since it was unaffected by atropine but abolished by mecamylamine, and a delayed secondary increase in discharge, due mainly to bronchoconstriction evoked by MCh. Physostigmine caused similar potentiation of responses to acetylcholine and MCh which implies that acetylcholinesterase is located close to the site(s) at which the drugs act to stimulate chemoreceptor activity. The findings are in agreement with the general principle that chemosensory activity is increased by nicotinic agonists but not by muscarinic agonists.

OBJECTIVE: Bronchial hyperresponsiveness is usually measured by bronchial challenge with direct (e.g. methacholine) and indirect (e.g. adenosine) agonists. A prospective, randomized, crossover, single-blind study was performed to compare both methods in the first diagnosis of asthma. PATIENTS AND METHODS: Fifty-seven patients, in which asthma was suspected, were selected (21 male, 36 female). Fifty-four underwent both challenges following the five-breath dosimeter protocol. PC20 was calculated according to ATS guidelines. Data of symptoms developed during the challenge, PC20 methacholine and adenosine, and FEV1 improvement after bronchodilator therapy were recorded. RESULTS: Symptoms at consultation were consistent with asthma in 68.4% patients, asthma and rhinitis in 29.8% and exercise-induced asthma in 1.8%. Atopy was reported in 93%; 49.1% had family history of atopy and 26.3% of asthma. The most frequent symptoms developed during the challenge were cough (40.4% with adenosine and 20.4% with methacholine) and wheezing (26.3% and 7.4% respectively), statistically significant differences. Bronchial challenge with MCh resulted positive in 44.4% of the patients and positive with AMP in 50%. Every patient with negative result to adenosine, was also negative to methacholine. In 94.4% subjects the result of both challenges was concordant (kappa index = 0.889). PC20 in both challenges showed poor linear correlation (Pearson r = 0.43, p < 0.05). Positivity of both challenges was only associated with having a positive skin prick test to danders (p = 0.001). Percentage of improvement after bronchodilator was 34.9% (SD12.2%) with adenosine challenge and 33.9% (SD17.9%) with methacholine (differences non statistically significant). CONCLUSIONS: Concordance in the result of both techniques is very high. Cough and wheezing are more frequent with adenosine, though not severe. PC20 with both techniques shows poor linear correlation.

Methacholine challenge testing (MCT), also sometimes described as bronchoprovocation testing, is widely performed for both research and diagnostic purposes. MCT is clinically useful when the patient presents with a history of symptoms suggesting asthma, but spirometry findings are normal. Typically, MCT is performed in a pulmonary function laboratory, a clinic, or a physician's office. MCT requires time, effort, and understanding. Two standard testing regimes are identified along with proper coding and reimbursement methodologies.

Bronchial hyperresponsiveness (BHR) is a common feature in the majority of asthmatic subjects and methacholine is the most frequently used agent for the test. The influence of 3 or 5 min time intervals between doses steps in a double methacholine challenge test (MCH-3' or MCH-5') was investigated. Using the MCH-3' challenge, 52 intermittent asthmatics were classified as having moderate (BHR-M; 18 subjects), mild (BHR-m; 19 subjects), or bordeline (BHR-B; 15 subjects) BHR. The cumulative dose and the PD20FEV(1) were higher for MCH-5' compared with MCH-3' in BHR-m (p < 0.05) and BHR-B (p < 0.05) but not in the BHR-M group. Also the dose response slopes, FEV(1)% decline/cumulative methacholine dose, calculated for the two challenge tests were statistically different only in BHR-m (p < 0.05) and BHR-B (p < 0.01). At MCH-5', there were 16 subjects with BHR-M, 18 with BHR-m, 12 with BHR-B and 6 subjects with normal reactivity. Results may suggest that in the group of BHR-m and BHR-B subjects, at MCH-5' compared with MCH-3', the cumulative effect of the administered drug, quickly metabolized by cholinesterase, is not complete, thus leading to an incorrect estimation of bronchial hyperresponsiveness degree. It is hoped that time interval between doses be standardized to ensure maximum comparability within and between subjects in challenge tests.

The present electrophysiological study shows that methacholine (MCh), generally regarded as a muscarinic agonist, stimulates the carotid chemoreceptors in pentobarbitone anaesthetized cats. The response consisted of a primary increase in discharge, attributable to nicotinic actions of MCh since it was unaffected by atropine but abolished by mecamylamine, and a delayed secondary increase in discharge, due mainly to bronchoconstriction evoked by MCh. Physostigmine caused similar potentiation of responses to acetylcholine and MCh which implies that acetylcholinesterase is located close to the site(s) at which the drugs act to stimulate chemoreceptor activity. The findings are in agreement with the general principle that chemosensory activity is increased by nicotinic agonists but not by muscarinic agonists.