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Chronic central nicotinic blockade after a single administration of the bisquaternary ganglion‐blocking drug chlorisondamine
Author(s) -
Clarke Paul B.S.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb16517.x
Subject(s) - chlorisondamine , nicotine , stimulant , pharmacology , nicotinic agonist , alkaloid , chemistry , ganglionic blocker , anesthesia , endocrinology , medicine , hexamethonium , acetylcholine , receptor , biochemistry , stereochemistry , blood pressure
1 Drug‐naive rats were tested for horizontal and vertical activity in photocell cages, for up to 80 min starting immediately after a subcutaneous injection of (−)−nicotine bitartrate or 0.9% w/v NaCl solution (saline). Nicotine (0.1 to 0.4 mg kg −1 base) depressed vertical activity and induced ataxia in the first 20 min, but increased both horizontal and vertical activity later in the session; these actions were dose‐dependent. A single intraventricular (i.v.t.) injection of chlorisondamine Cl (2 μg base), a quaternary ganglion‐blocking drug, given one to two weeks before testing, blocked the ataxic and stimulant actions of nicotine. 2 The antagonistic actions of chlorisondamine (0.2, 1.0, 5.0 μg i.v.t., single administration) were shown to be dose‐dependent. The stimulant actions of nicotine were blocked in a dose‐dependent way for the duration of the experiment (5 weeks); nicotine's depressant actions were completely blocked at two weeks but not at five weeks. 3 A ganglion‐blocking dose of chlorisondamine (0.1 mg kg −1 ), given subcutaneously (s.c.), failed to reduce the behavioural actions of nicotine, whereas a much higher systemic dose (10 mg kg −1 s.c.) was effective for at least five weeks. 4 Chlorisondamine failed to alter the behavioural effects of (+)‐amphetamine or apomorphine, while blocking those of nicotine. 5 It is concluded that chlorisondamine antagonizes some of nicotine's central actions in a potent, long‐lasting and pharmacologically selective way.