DESOXYPEGANIN - Synthese, Metabolismus und Darreichungsformen

Desoxypeganine (1,2,3,9-Tetrahydropyrrolo[2,1-b]-quinazoline) is an alkaloid isolated from Peganum harmala L. / Zygophyllaceae. The substance causes depression of monoaminoxidase and inhibition of acetylcholinesterase two times superior than galanthamine in spite of being less toxic. These effects allow a large variety of therapeutic uses such as nicotine dependence as well as alcoholism. Desoxypeganine can also slow down the progression of AlzheimerŽs disease and improve mental cognitive capabilities. In this dissertation Desoxypeganine was completely characterised, starting with developing a facile synthesis without production steps like distillation and the use of chlorinated solvents. Further the behaviour from Desoxypeganine against oxidation was shown, the metabolites from aerobic incubation of 9000 g supernatant of rabbit liver homogenates as enzyme source were specified by using LC-MS, the isoenzyme CYP 2D6 was identified as the main metabolising enzyme of Desoxypeganine with the supernatant of a human liver and the Km as well as the Vmax value were determined. A complete characterisation of a new active substance contains also the development of pharmaceutical forms. After the production of Desoxypeganine salts with microscopic and macroscopic considerations, tablets as the most common form were produced and described. A second pharmaceutical form, a transdermal patch, was developed with different adhesive agents and enhancers to minimize the first pass effect. The permeation value was tested over human skin and quantified by means of HPLC. This dissertation shows a complete characterisation of Desoxypeganine by collecting many informations from all the different topics of pharmacy. These informations should serve as orientating informations for the planned clinical studies.