Differences of sympathomimetic and anticholinergic action of OH-maprotiline and its R (-)-enantiomer.
1 C 49802 B-Ba and CGP 12103/A are the racemate and the R (-)-enantiomer respectively of the hydroxylated derivative of the tetracyclic antidepressant maprotiline, which differed in their ability to block noradrenaline-uptake and in their anticholinergic activity in animal models. 2 The sympathomimetic and anticholinergic activities of both substances were evaluated in eight healthy subjects and compared with the treatment with placebo and amitriptyline. 3 Heart rate, pupillary diameter, stimulated salivary flow rate and blood pressure were measured over a 15 h period keeping a very strict protocol. Plasma catecholamine levels were determined. 4 Saliva production was diminished following the administration of C 49802 B-Ba, CGP 12103/A and amitriptyline. 5 A moderate, but significant increase in heart rate and mean arterial blood pressure in the recumbent position was observed when C 49802 B-Ba was given. 6 The results in man are in agreement with the different activities found in animal experiments. 7 It can be concluded that the S (+)-enantiomer which the racemate contains is more active than the R (-)-enantiomer as to the anticholinergic and the sympathomimetic property.
D000328:Adult; D000873:Anthracenes / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008376:Maprotiline / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology*; D010276:Parasympatholytics; D011680:Pupil / Q000187:drug effects; D012472:Salivation / Q000187:drug effects; D013237:Stereoisomerism; D013566:Sympathomimetics; D013997:Time Factors
D000873:Anthracenes; D002395:Catecholamines; D010276:Parasympatholytics; D013566:Sympathomimetics; D008376:Maprotiline; C027299:hydroxymaprotilin