RAPID DISTRIBUTION OF TRYPTOPHOL (3-INDOLE ETHANOL) TO THE BRAIN AND OTHER TISSUES

Tryptophol (3-indole ethanol) is a compound which induces sleep and is formed in the liver after disulfiram treatment and by the parasite Trypanosoma brucei gambiense in trypanosomal sleeping sickness. Radiolabeled tryptophol was prepared, purified and characterized for the purpose of defining its tissue distribution in animals. Tryptophol was highly lipophilic, with an octanol:water partition coefficient of 29.8. Brain extraction, determined after intracarotid injection [rats], was high (brain uptake index = 117 .+-. 3.5%) and nonsaturable, suggesting the absence of a carrier system. After i.v. administration, tryptophol distribution to tissues correlated with relative blood flow. More than 85% of the radioactivity remaining in brain 2-5 min after i.v. injection co-migrated with tryptophol standards when analyzed by TLC. Tryptophol apparently binds to serum and in vivo may be stripped from serum albumin and taken up by brain in a single capillary transit. In states such as trypanosomal sleeping sickness or disulfiram treatment, remotely formed tryptophol probably gains ready access to brain (it is 100% cleared in a single capillary passage) and may cause somnolence.