H/D Exchange for 4-Aminopyridine: Application on MAO in Sera of Multiple Sclerosis Patients

Abstract

Multiple sclerosis (MS) is a neurological disorder characterized by a complex array of symptoms affecting
movement and the senses. It is an inflammatory disease of the central nervous system (CNS) causes an injury
in the myelin sheaths, leading to demyelination and thus, consequently, a series of neurologically dysfunction
known as relapses. 4-Aminopyridine is used in the treatment of MS patients as a selective voltage blocker
channel. The study designed over two stages, first 4-aminopyridine went under H/D exchange, and then
both deuterated and non-deuterated 4-AP was applied on the serum of MS patients and the activity of serum
monoamine oxidase was estimated. The study included 120 subject which divided over two groups, control
and MS patients, each of which contain 60 subject. The activity of MAO was significantly (P<0.01) higher
in patients than that of control. The activity of MAO activity has decreased significantly (P<0.01) in the
presence of 4-AP, as well as a further significant decrease in the presence of deuterated 4-AP. In conclusion,
4-AP has inhibitory effect on MAO activity, and the replacement of hydrogens with deuterium gives an
enhancement on this inhibitory effect.