Methacholine, Long-acting M-cholinolytic and beta2-agonist on the Activity of Beta-receptors in Healthy Volunteers

Methacholine, Long-acting M-cholinolytic and beta2-agonist on the Activity of Beta-receptors in Healthy Volunteers

Effect of Methacholine, Long-acting M-cholinolytic and beta2-agonist on the Binding Activity of Beta-receptors in Healthy Volunteers

Moscow State University of Medicine and Dentistry, National Medical Research Center for Cardiology, Ministry of Health of Russian Federation, Branch of Shemyakin-Ovchinnikov Institute of Bioorganic chemistry of RAS

Interventional open-labeled study in parallel groups is aimed to evaluate changes of beta receptors in healthy volunteers under the influence of inhaled metacholine, long-acting anticholinergics and beta-agonists using modified radioligand method.

Long-acting beta2-agonists and anticholinergics are main drugs in therapy of chronic obstructive pulmonary disease . Beta-agonists exert their bronchodilatory effects via β2 adrenoceptors located on airway smooth muscle cells. Anticholinergics block mainly M3-cholinoreceptors located in the airways, thus inhibiting bronchoconstriction. Metacholine blocks M2-cholinoreceptors thus inducing bronchoconstriction. It is known, that muscarine and beta-receptors interact with each other, but the detailed mechanism is unknown. For evaluating the binding activity of beta-receptors after inhalation of these drugs the modified radioligand method was used.

There are two groups: the first group is smokers, the second group is non - smokers. The participants of both groups will receive metacholine on the first visit, formoterol 12 micrograms on the second visit, then tiotropium bromide 18 mkg on the third visit.

Change from baseline beta-receptor binding activity at 60 min after the inhalation of formoterol or tiotropium.

Beta-receptor binding activity will be measured with modified radioligand method before and after 60 min after the inhalation of formoterol or tiotropium

Change from baseline beta-receptor binding activity at 40 min after the challenge test with metacholine.

Beta-receptor binding activity will be measured with modified radioligand method before and after 40 min after the challenge test with metacholine.

Comparison of beta-receptor binding activity measured with modified radioligand after formoterol and tiotropium.

Difference of change of beta-receptor binding activity measured with modified radioligand method before and after 60 min after the inhalation of formoterol and tiotropium.

Comparison of beta-receptor binding activity measured with modified radioligand method after formoterol or tiotropium in smokers and non-smokers.

Difference of change of beta-receptor binding activity measured with modified radioligand method before and after 60 min after the inhalation of formoterol or tiotropium in smokers and non-smokers.

Difference of change of beta-receptor binding activity measured with modified radioligand method before and after inhalation of metacholine

Comparison of beta-receptor binding activity measured with modified radioligand method after inhalation of metacholine in smokers and non-smokers.

Difference of change of beta-receptor binding activity measured with modified radioligand method before and after inhalation of metacholine

Inclusion Criteria: 1 Provision of signed and dated informed consent form 2. Healthy male or female, aged 18-60 years Exclusion Criteria: Participants unable to perform spirometry Exacerbation respiratory infection within the previous four weeks Hypersensitivity or allergy to formoterol, metacholine or tiotropium bromide Females who are currently pregnant and lactating major surgery in the last 6 months Refusal to participate Currently participating in another clinical study

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Smolyakova E.V., Skoblov Y.S., Skoblova N.A., Agapova O.Y., Ambat'ello L.G., Klimova A.A., Kuznetsova T.V., Masenko V.P., Nistor S.Yu., Rvacheva A.V., Chazova I.E., Zykov K.A. Specificity and Selectivity of the Modified Radioligand Method for Assessment of β1-Adrenoreceptor's Binding Activity on Human T-Lymphocytes. Russian Journal of Bioorganic Chemistry 45(3): 295-301, 2019