Synthesis and Investigation of 2-Propylpentanoyl Amino Acid and Dipeptide Conjugates as Novel Anticonvulsants

doi:10.21608/ejchem.2010.1222

Synthesis and Investigation of 2-Propylpentanoyl Amino Acid and Dipeptide Conjugates as Novel Anticonvulsants

10.21608/ejchem.2010.1222

Abstract

THE CENTRAL nervous system (CNS) requires the anticipation of a number of neuro-active amino acids and peptides(1) for its normal function. Thus, - aminobutyric acid (GABA), glycine, histadine, tyrosine, arginine, taurine, aspartic and glutamic acids, are involved in the synthesis of neurotransmitters neuromodulators, or their neuro-agonists. In particular, glycine is an inhibitory neurotransmitter(1) that is found in mammalian proteins and tissues. Its role primarily appears to involve the inhibition of neuronal activity in the striatum, substantia nigra and cerebellum. Analougously, -aminobutyric acid (GABA)(2) is a constituent of mammalian tissues particularly the brain and spinal cord. It is synthesized in GABA ergic neurons, and interacts with postsynaptic receptors to exert its inhibitory effects.
On the other hand, the collective terms “convulsive disorders”, “seizure disorders” and “cerebral seizures” are currently, synonymously considered, for epileptic convulsions. Such disorders are common neurological symptoms of a complex nature and, frequently, undetermined etiologies.
With the existing medications, however, approximately 25% of epileptic patients are not seizure free, regardless of their therapy optimization. In addition to the apparent health hazards, considerable socio-economic problems are intrinsically encountered with the prevalence of untreated epilepsy.
In that context, 2-propylpentanoic acid (
generic name: Valproic Acid (trade names: Depakene®,“Abbott Lab”) is one of the essential antiepileptics, that are still predominant in the current clinical practice(3).