[Effects of methanobenzazonine (2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine) derivatives on the cough reflex and respiration].
Antitussive and respiratory effects of three newly synthesized methanobenzazonine derivatives and their d- and l-isomers were investigated to understand the relationship between the cough and respiratory centers. Antitussive effects were evaluated with the PEC (puncture electrode-induced cough) method in conscious d-, dl-, and l-ST-2123; d-, dl-, and l-ST-2121 into the right carotid artery at a dose range of 0.2-0.8 mg caused no effect on respiration. dl-ST-2121 at 0.4 to 0.8 mg and l-ST-2121 at 0.2 to 0.8 mg depressed respiration dose-dependently. Codeine (0.2-0.8 mg) depressed respiration slightly. Morphine (0.2-0.8 mg) depressed respiration more strongly. All the methanobenzazonine derivatives used, when given intraperitoneally, showed antitussive potencies that were 1/3-1/2 the potency of codeine. The antitussive potencies of the d-, dl-, and l-isomers of the three derivatives used were discussed on the bases of chemical structures and drug receptors. These results provide evidence of a discrepancy between the cough and respiratory centers in the brain stem.
D000818:Animals; D000996:Antitussive Agents; D001381:Azepines / Q000494:pharmacology*; D003371:Cough / Q000188:drug therapy*; D006168:Guinea Pigs; D007536:Isomerism; D008297:Male; D009904:Optical Rotation; D012018:Reflex / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000996:Antitussive Agents; D001381:Azepines; C024677:eptazocine hydrobromide