Comparison of radioreceptor assay and radioimmunoassay for atropine: Pharmacokinetic application

Abstract

A membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist quinuclidinyl benzilate (QNB). The KD for binding was 0.48 nM and Bmax was 1.42 pmol/mg protein. Atropine competitively inhibited the binding of tritiated QNB to muscarinic receptors. This new radioreceptor assay (RRA) for atropine has been compared with a radioimmunoassay (RIA) for atropine. The RRA measures only the active component of atropine, 1-hyoscyamine and in this respect it differs from the RIA. As little atropine as 1.25 ng/ml (4.33 nmol/l) in a 25 microliters serum sample could be reliably assayed by the RRA. Using both assay techniques the pharmacokinetics of atropine was studied after a single 0.02 mg/kg i.v. dose given to 8 anaesthetized patients. The half-life calculated by the RRA was 3.7 +/- 2.3 h (m +/- SD) and by the RIA 4.3 +/- 1.7 h. Both the volume of distribution and the total clearance were higher according to the RRA than the RIA: 3.9 +/- 1.5 vs 1.7 +/- 0.71/kg and 15.4 +/- 10.3 vs 5.9 +/- 3.6 ml/min/kg, respectively. The AUC measured by the RRA and RIA was 29.8 +/- 18.9 and 103.9 +/- 110.7 micrograms X h/l, respectively. The differences in the pharmacokinetics according to the 2 methods are presumably due to preferential tissue uptake of the l-form.

Carotid-Cardiac Baroreflex Function Does Not Influence Blood Pressure Regulation during Head-Up Tilt in Humans

“…This finding was consistent with the studies that used atropine sulphate to induce vagal blockade [31,39]. Atropine sulphate crosses the blood barrier [10,11], blocking central muscarinic cholinergic receptors, which results in the removal of its central inhibitory influence on muscle sympathetic nerve activity [13,40]. However, the LF power of blood pressure variability was not related to the muscle sympathetic nerve activity [41], but the LF pulse interval variability and the LF power of the blood pressure variability were correlated [31,42].…”

“…Following one hour of recovery in the supine position, the protocol was repeated after an administration of repeated small (0.2 mg) intravenous doses of glycopyrrolate until there was no further increase in HR (group average dose of 12.0 ± 1.0 µg/kg body weight; range of 8.6-16.9 µg/kg body weight). We used glycopyrrolate to affect cholinergic blockade instead of the more commonly used atropine sulphate because atropine sulphate crosses the blood-brain barrier and influences central muscarinic receptors [10,11], confounding the interpretation of responses exhibited in the systemic circulation [12,13].…”

HPLC–atmospheric pressure chemical ionization mass spectrometric method for enantioselective determination of R,S-propranolol and R,S-hyoscyamine in human plasma

“…In contrast to Prop, the volumes of distribution at steady-state for Hyosc enantiomers were similar (V ss /f = 7.82 ± 2.66 L/kg vs. 7.73 ± 1.39 L/kg). These trends are consistent with the pharmacokinetic study reported by Aaltonen and co-workers, where either S-Hyosc or Hyosc were measured with radioreceptor assay or radioimmunoassay, respectively [42]. They reported stereospecific differences in pharmacokinetics of R-and SHyosc with more than three times smaller AUC for S-Hyosc in comparison to Hyosc.…”

Anticholinergic activity in the serum of patients receiving maintenance disopyramide therapy.

“…The serum levels of anticholinergic activity in the same samples were determined by a radioreceptor assay according to Aaltonen et al (1983). The incubation medium (300 ,ul) Aaltonen & Scheinin (1982).…”