Abstract: The novel compounds of formula: ##STR1## in which R is isopropyl, cyclohexyl, phenyl, CH.sub.3, Br or I; or H R.sub.1 is CH.sub.3 or cyclopropyl and R.sub.2 is H or Br, and when R.sub.1 is cyclopropyl and R.sub.2 is H, R is other than H, and when R.sub.1 is CH.sub.3 and R.sub.2 is H, R is other than H, and when R.sub.1 is CH.sub.3 and R.sub.2 is H, R is other than I, and when R is CH.sub.3 and R.sub.2 is H, R.sub.1 is other than CH.sub.3, and when R is phenyl and R.sub.2 is H, R.sub.1 is other than CH.sub.3, exhibit superior activity in the treatment of pathologies which interfere with the circadian rhythm. A novel method of preparation is described according to which the pharmaceutical compositions containing the novel compounds, as well as compounds already known, are administered transdermally. The novel method of administration results in sustained peripheral blood level. Novel pharmaceutical compositions are described suitable for transdermal administration.

Abstract: A method of synthesizing an indole derivative of the tryptamine type particularly .?.melatonine,.!. .Iadd.melatonin .Iaddend.comprising the steps of 1) reacting potassium phthalimide and 1,3-di-bromopropane to obtain 3-bromopropylphthalimide; 2) reacting 3-bromopropylphthalimide with sodium acetoacetic ester in ethanol to obtain ethyl-2-acetyl-5-phthalimidopentanoate; 3) reacting the product from step 2) with diazo-p-anisidine to obtain 2-carboxyethyl-3-(2-phthalimidoethyl)-5-methoxy-indole; 4) reacting the 2-carboxyethyl-3-(2-phthalimidoethyl)-5-methoxy-indole with 2N/NaOH and then 20% H.sub.2 SO.sub.4 to obtain impure 5-methoxytriptamine, which is purified by means of hexamethyldisilazane. The mono and disubstituted derivatives are obtained and the monosubstituted derivative is hydrolyzed with aqueous methanol and then recrystallized from ethanol. The N-acetyl derivative is prepared by reaction with acetic anhydride. .?.Melatonine.!. .Iadd.Melatonin .Iaddend.