Quaternary ammonium glucuronides

Kaku T et al (2004) Quaternary ammonium-linked glucuronidation of tamoxifen by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem Pharmacol 67 2093-2102... 

Remmel RP, Sinz MW. A quaternary ammonium glucuronide is the major metabolite of lamotrigine in guinea pigs. In vitro and in vivo studies. Drug Metab Disp 1991 19(3) 630-636. 

Antimuscarinics having a quaternary ammonium group are incompletely absorbed from the gut since these are completely ionized. The tertiary amine antimuscarinics are readily absorbed from the gut. The presence of food may reduce absorption. Quaternary ammonium antimuscarinics exhibit poor lipid solubility, do not cross the blood-brain barrier, and thus exhibit minimal central nervous system (CNS) effects. Also due to their poor lipid solubility they do not penetrate the eye and are unlikely to appear in the milk. Atropine and other tertiary amines are capable of crossing the CNS. Atropine is capable of crossing the placenta and has been stated to distribute into milk in small quantities. It is oxidized primarily in the liver. Atropine is apparently metabolized in the liver to tropic acid, tropine, and possibly esters of tropic acid and glucuronide conjugate. 

Figure 21 Examples of unusual glucuronidation reactions lamotrigine (quaternary ammonium glucuronide) and sulfinpyrazone (carbon-linked glucuronide). ...

Identification of a quaternary ammonium-linked glucuronide of chlorpromazine in the urine of a schizophrenic patient treated with chlorpromazine. Drug Metab Dispos 16 506-508, 1988. 

H Luo, EM Hawes, G McKay, ED Korchinski, KK Midha. The quaternary ammonium-linked glucuronide of doxepin A major metabolite in depressed patients treated with doxepin. Drug Metab Dispos 19 722, 1991. 

MW Sinz, RP Remmel. Isolation and characterization of a novel quaternary ammonium-linked glucuronide of lamotrigine. Drug Metab Dispos 19 149, 1991. 

Green, M. D., Bishop, W. R, and Tephley, T. R., Expressed human UGT1.4 protein catalyzes the formation of quaternary ammonium-linked glucuronides. Drug Metab. Dispos., 23 299-302, 1995. 

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