A Comprehensive Monograph on L-Cycloserine (Levcycloserine): Pharmacology, Stereochemistry, and Therapeutic Potential

Executive Summary

1.1. Introduction to L-Cycloserine

L-Cycloserine, also known by the International Nonproprietary Name (INN) Levcycloserine, is the (S)-enantiomer of the broad-spectrum antibiotic cycloserine.[1] Identified by the Chemical Abstracts Service (CAS) number 339-72-0 and DrugBank accession ID DB17627, this small molecule represents a case study in pharmacological stereospecificity. It is imperative to distinguish L-Cycloserine from its more widely known (R)-enantiomer, D-Cycloserine (DrugBank ID DB00260), which is marketed under brand names like Seromycin® and is clinically employed as a second-line agent for treating drug-resistant tuberculosis.[3] A significant portion of the publicly available scientific and medical literature conflates the two isomers or uses the term "cycloserine" generically, leading to considerable confusion regarding their distinct pharmacological profiles, mechanisms of action, and therapeutic potential. This report aims to provide a definitive and comprehensive analysis of L-Cycloserine, clarifying its unique properties in contrast to its clinically utilized stereoisomer.

1.2. Core Pharmacological Profile

The defining pharmacological characteristic of L-Cycloserine is its function as a potent and irreversible inhibitor of the enzyme serine palmitoyltransferase (SPT), also known as 3-ketodihydrosphingosine synthetase (EC 2.3.1.50).[2] SPT catalyzes the initial and rate-limiting step in the

de novo biosynthesis of ceramides and all downstream sphingolipids, which are critical components of cell membranes and signaling molecules. The stereospecificity of this action is profound; L-Cycloserine is approximately 100 times more potent in its inhibition of SPT than D-Cycloserine, a distinction that underpins its unique therapeutic and toxicological profile.[2]