Improved delivery through biological membranes. Synthesis, distribution, and neurochemical effects of a tryptamine chemical delivery system.

Enhanced central delivery of tryptamine was proposed by application of a dihydropyridine in equilibrium pyridinium salt redox system. This drug delivery method, which relies on biochemistry similar to that which occurs in the NAD+ in equilibrium NADH coenzyme system, required synthetic derivatization of tryptamine. When the resulting tryptamine chemical delivery system (TCDS) was systematically administered, it passed the blood-brain barrier intact and then oxidized. The resulting quaternary form (TQ+) accumulated in the brain of rats relative to most peripheral organs. The only organ in which a more rapid efflux was not demonstrated was the heart. Intestinal administration of the TCDS showed the ability of the system to undergo absorption and to survive the first pass through the liver. The TCDS caused central neurochemical changes consistent with central delivery of tryptamine. Possible applications of the TCDS are discussed.