James G. Henkel

Pharmacological activity of amantadine: effect of N-alkyl substitution

Alkyl substitution on the nitrogen atom of the anti‐parkinsonian drug amantadine resulted in changes in its pharmacological potency. Greater behavioural stimulation (i.e. increased motor activity) was observed following s.c. injection of several of the analogues, with optimal activity produced by N‐n‐propyl substitution. These molecular changes did not alter the activity of amantadine on inhibition of dopamine uptake or its weak affinity for dopamine receptors in‐vitro. Several of the analogues were more effective than the parent compound in increasing the concentration of dopamine metabolites (suggesting an increase in dopamine utilization) following systemic injection, and these effects generally followed the same pattern as observed in the test of behavioural activity. These results provide further support for the concept that the activity of amantadine may be improved by molecular alterations, although the pharmacological basis for this activity remains obscure.

The Preparative Scale Reverse Phase HPLC Separation of Epimeric Alkaloids Using Camphorsulfonic Acid as an Ion Pairing Reagent

Abstract A reverse phase paired ion HPLC procedure is described for the separation of multigram quantities of epimeric alkaloids using camphorsulfonic acid as the ion-pairing reagent.

A substrate-directed synthesis of substituted 2-azaadamantanes

Abstract A synthesis of mono- and disubstituted 2-azaadamantanes with control of substituent stereochemistry has been developed.