Intestinal absorption of tetramethylammonium and its derivatives in rats.

The disappearance kinetics of the acetylcholinesterase inhibitor galanthamine hydrobromide from the gastrointestinal tract of male Wistar rats, 200-250 g, in-situ has been examined. After 30 min the galanthamine loss was 16% in the stomach (pH 2), 54-85% in the duodenum and the successive small intestinal segments (pH 6.8), 43% in the colon and 76% in the rectum. Compared with the other segments, the disappearance rate was higher in the terminal ileum (0.38 x 10(-2) mg cm-1 min) and in the rectum (1.27 x 10(-2) mg cm-1 min). In the proximal jejunum, terminal ileum and rectum the disappearance rate was linearly dependent on the galanthamine dose (range 0.5-4 mg, 2-16 mg kg-1). The results suggest that when administered orally, rapid galanthamine absorption could be expected all over the gastrointestinal tract due mainly to the passive diffusion mechanism.

Section: Discussionmentioning

confidence: 99%

Gastrointestinal loss of galanthamine hydrobromide in rats in-situ

Yamboliev

Mutafova‐Yambolieva

Mihailova

1993

“…It may be assumed that QACs without a hydrophobic part would be absorbed from the intestine with difficulty. However, some investigators have pointed out that small-molecular QACs such as choline and tetramethylammonium (TMA) are well absorbed, and that carrier-mediated transport systems participate in their membrane transport (Sanford & Smyth 1971;Kuczler et a1 1977;Kessler et al 1978;Hegazy & Schwenk 1984;Tsubaki & Komai 1986). Recently, we have found that the transport mechanism of paraquat, a harmful bis-QAC, is different from that of a large QAC, with a hydrophobic part; initial uptake of paraquat by the brush border membrane vesicles is significantly inhibited by choline and TMA (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal absorption of quaternary ammonium compounds correlated to their binding to small intestinal brush border membrane in rat

Shinmoto

Saitoh

Iseki

et al. 1991

The relationship between absorption of quaternary ammonium compounds (QACs) from rat intestine and their in-vitro binding to isolated brush-border membrane has been examined, using a series of n-alkyltrimethylammoniums. The binding of these QACs gradually increased with each extension of unbranched hydrocarbon chain from octyltrimethylammonium to tetradecyltrimethylammonium. However, hexyltrimethylammonium and heptyltrimethylammonium failed to bind to the membrane. On the other hand, the disappearance of these QACs from rat jejunal loop also increased with the length of hydrocarbon chain over the range of 8.9 to 71.3%. A good correlation was found between binding to the brush-border membrane and disappearance from jejunal loop. From these results, it was suggested that the size of the hydrophobic part of a QAC molecule was a principal determinant of both absorption and membrane binding, and that the absorption of QACs with an appropriate sized hydrophobic part, was closely associated with the degree of binding to the membrane.

“…In this study, we have demonstrated that both hydrophobic and hydrophilic components are significant factors in the determination of binding properties in rat small intestinal brush border membrane. Tetramethylammonium, tetraethylammonium and choline are absorbed through the rat small intestine by a common carrier-mediated transport system (Tsubaki & Komai 1986). In the present study, these compounds did not bind to brush border membrane sufficiently to inhibit methylchlorpromazine binding.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Structures of Organic Cations and Their Binding Behaviours to Brush Border Membrane Isolated from Rat Small Intestine

Shinmoto

Noujoh

Chiba

et al. 1990

We have investigated the correlation between the molecular structures of various organic cations and their binding to rat small intestinal brush border membrane. The binding of small quaternary ammonium compounds such as tetramethylammonium and choline to brush border membrane was not sufficient to inhibit methylchlorpromazine binding. However, lauryltrimethylammonium and cetyltrimethylammonium, both quaternary amines with a long carbon chain, inhibited binding significantly. The inhibition was competitive. When the unbranched hydrocarbon chain of the quaternary amines was extended in steps from C1 (methyl) to C16 (cetyl), the inhibitory effect increased sharply with length from C7 (heptyl) to C16. These results suggest that the size of the hydrophobic part of the molecule is an important factor in binding of quaternary ammonium compounds to the brush border membrane. The structure of the hydrophilic part was another factor. In imipramine-related compounds, the order of binding was N-didesmethylimipramine (primary amine) greater than desipramine (secondary) greater than imipramine (tertiary) greater than methylimipramine (quaternary). However, with the small molecular ethylamine-related compounds, binding properties did not reflect differences in the hydrophilic component. Therefore, the effect of the hydrophilic part may be secondary and may depend on the size of the hydrophobic part. We suggest that organic cations which are amphiphilic can bind to a common binding site on brush border membrane through hydrophobic and/or hydrophilic interactions.