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How were the properties of bile acid sequestrants like cholestyramine discovered? The earliest reference to the chemical I could find was the following article which does not discuss the history of the drug:

Glueck CJ, Fallat R, Tsang R. Pediatric familial type II hyperlipoproteinemia: therapy with diet and cholestyramine resin. Pediatrics. 1973; 52:669-79. [IDIS 37416] [PubMed 4355362]

Does this kind of drug exist in nature or is it purely synthetic?

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It is definitely synthetic, a trimethyl-ammonium derivative of polystyrene.

The first to use it as a human medication seems to be Stanley S. Bergen, Jr. et al.

See Effect of an Ion Exchange Resin on Serum Cholesterol in Man Proceedings of the Society for Experimental Biology and Medicine, Volume 102, 1959, Pages 676–679:

It is well known that bile acids are a major end product of cholesterol metabolism and that cholesterol is probably the only precursor of bile acids([references]1-3 ) . Rate of oxidation of cholesterol to bile acids is believed to be regulated by need for bile acids for digestive purposes, cholesterol normally being oxidized at a rate sufficient to replace the bile acid that escapes reabsorption and is lost in the feces ([references] 4 - 5). If an agent could be found that would sequester bile acids and thereby promote their excretion in the feces, 2 consequences of clinical interest might be anticipated: (1) increase in rate of oxidative degradation of cholesterol. and (2) decrease in serum cholesterol level. Tennent ([reference] 6) described lowering of serum cholesterol levels in animals fed the chloride salt of a basic anion exchange resin. This material (MK-135) has marked affinity for bile acids in vitro and is believed to exert its serum cholesterol-lowering effect by virtue of this property( 6 ) . The present report summarizes results obtained when MK 135 was administered to 26 patients, many with elevated serum cholesterol levels.

Reference 6 is Tennent, D. M., Siegel, H., Zanetti, M. E., Kuron, C. W., Ott, W. H., Wolf, F. J., Circulation, 1959, v20, 996.

Even though Bergen's paper only uses the term "MK 135", according to the editor's note on the current online version, this paper is the first use of cholestyramine as a medication in humans.

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