Metabolism of dimethylamine in the nasal mucosa of the Fischer 344 rat.
The metabolism of dimethylamine (DMA) in the nasal mucosa of the male Fischer 344 rat was investigated in vitro and in vivo. Microsomes were prepared from liver, and from respiratory and olfactory nasal mucosa. All microsomal preparations metabolized DMA to formaldehyde (CH2O), though DMA was a poor substrate for the N-demethylation reaction when compared to benzphetamine. Phenobarbital-induced microsomes metabolized DMA at a rate less than that of control. The results indicated that DMA was a substrate for both cytochrome P-450 and FAD-containing monooxygenase, and that both enzyme activities were present in all microsomal preparations. Finally, unextractable radioactivity was observed in DNA, RNA, and protein isolated from respiratory and olfactory mucosa of rats exposed to either 10 or 175 ppm of [14C]DMA, suggesting metabolism of [14C]DMA to 14CH20 with subsequent incorporation of 14C into macromolecules. The results demonstrate that the respiratory and olfactory nasal mucosa have the capability to metabolize DMA to CH2O, and indicate that such metabolism occurs in vivo.
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001589:Benzphetamine / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004123:Dimethylamines / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D000814:Aniline Compounds; D004123:Dimethylamines; D001589:Benzphetamine; C015157:N,N-dimethylaniline; D003577:Cytochrome P-450 Enzyme System; C034516:dimethylamine; D010634:Phenobarbital