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Updated: Aug 19, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
Published on: February 11, 2019
[Experimental studies on the question of an adjuvant function of bromhexine]
Abstract:
On a possible adjuvant function of a bronchosecretolytic preparation commercially available, N-cyclohexyl-N-methyl-(2-amino-3,5-dibromobenzyl)-amine-hydrochloride (bromhexine, Bisolvon-R), sensibilization tests on 30 rabbits were undertaken. 5 animals received Bisolvon and human albumin as antigen, 5 rabbits human albumin only, 5 rabbits Bisolvon and human lymphocytes, 5 rabbits human lymphocytes only, 5 rabbits Bisolvon alone, and 5 received neither Bisolvon nor any antigen. The techniques in these studies, such as two-dimensional double immunodiffusion in agar gel, lymphocytotoxicity test, mixed lymphocyte culture test, electrophoresis on cellulose-acetate foil were used as well as histologic preparations. It could be ascertained that sensitizing with human albumin and simultaneous application of Bisolvon led to a higher concentration of antibodies against albumin than did sensitizing with human albumin alone. Rabbits sensitized with human lymphocytes showed no obvious difference in their antibody rates whether they had received Bisolvon or not. This applied to cell mediated antibodies as well as to the rate of cytotoxic antibodies against human lymphocytes. Among the histologic findings of spleen, bone marrow showed the morphologic equivalences expected from xenosensitization. Comparing the results of sensitized rabbits with and without Bisolvon there were no positive differences as to intensity and/or type of reactivity to be seen. Liver and kidney showed no considerable pathologic phenomena with the exception of some cases with coccidiosis in the bile ductuli. Concerning the bronchial mucosa, in all rabbits treated with Bisolvon an increase of mucine enriched goblet cells as well as a hypergranulation of different epithelial cell types could be observed. Moreover in all animals, including the controls, an intense lymphatic infilitration in the subepithelial and submucous area was identified. The increased antibody concentration in the sera of animals from group I compared with that of rabbits from group II is interpreted as an enhancement of cell membrane's permeability effected by bromhexine. By this mechanism, on one hand antigen molecules could be absorbed better, while on the other elimination of molecular antibodies, that means immunoglobulins, from plasma cells could be favoured.
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