Mecamylamine absorption

Mecamylamine, a secondary amine, was developed to improve the degree and extent of absorption from the gastrointestinal tract because the quaternary amine ganglion-blocking compounds were poorly and erratically absorbed after oral administration. Trimethaphan, a short-acting ganglion blocker, is inactive orally and is given by intravenous infusion. 

Mecamylamine [mek a MILL a meen] produces a competitive nicotinic block of the ganglia. The duration of action is about 10 hours after a single administration. The uptake of the drug via oral absorption is good in contrast to trimethaphan. 

This reasoning led to the development of mecamylamine by Stone and his associates (19). Mecamylamine is not a quaternary base but rather a secondary amine which permits complete absorption from the gastrointestinal tract. This modification unfortunately did not strikingly improve therapeutic effectiveness (8). Clinical trials soon showed that the fluctuating blood pressure response associated with the ganglion-blocking agents was not due primarily to variable absorption. 

Absorption of mecamylamine is less erratic, but reduced bowel activity and paralytic ileus are a danger. After absorption, the quaternary ammonium- and sulfonium-blocking agents are confined primarily to the extracellular space and are excreted mostly unchanged by the kidney. Mecamylamine concentrates in the liver and kidney and is excreted slowly in an unchanged form. 

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