Airway smooth muscle relaxant effects of the cocaine pyrolysis product, methylecgonidine.
Methylecgonidine (anhydroecgonine methylester; MEG) is produced when cocaine base ("crack") is heated. Since crack smoking can produce significant airway toxicity and the role of MEG in this toxicity is unknown, we determined the effects of MEG on guinea pig isolated tracheal rings. Trachea do not contract in response to MEG; rather, MEG (10(-9) to 10(-3) M) dose-dependently relaxed tissue precontracted with 2 x 10(-3) M acetylcholine (ACh). MEG (10(-9) to 10(-6) M) reduced the magnitude of contractions induced by ACh, carbachol, histamine and KCl in a nonsurmountable manner; the maximal response to these agents was not restored after repeated washing. MEG did not affect contractions induced by BaCl2. 4-Diphenyl acetoxymethyl piperidine methiodide (4-DAMP; 10(-7) M), in the presence or absence of MEG (10(-7) M), shifted the dose-effect curve for ACh 30-fold to the right. After washing, sensitivity to ACh was fully recovered in tissues exposed to 4-DAMP alone, but was still reduced to 50% of control in tissues exposed to 4-DAMP and MEG. The effects of MEG were unlike those of cocaine which, at 10(-7) to 10(-5) M, increased the magnitude of contractions induced by ACh (10(-9) to 2 x 10(-3) M); MEG (10(-7) M) abolished this increase. The mechanism by which MEG relaxes tracheal smooth muscle has not been established, but it is likely to be independent of direct interaction with sites that mediate the effects of the bronchoconstrictor agents used in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
el-Fawal
H A
HA
Department of Environmental Medicine, New York University Medical Center, New York.
Wood
R W
RW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents; D002217:Carbachol / Q000494:pharmacology; D002645:Chickens; D003042:Cocaine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006358:Hot Temperature; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects*
D001993:Bronchodilator Agents; C068464:anhydroecgonine methyl ester; D006632:Histamine; D002217:Carbachol; D003042:Cocaine; D000109:Acetylcholine