Chloroquine (DB00608): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Chloroquine is a synthetic 4-aminoquinoline derivative that has occupied a multifaceted and often paradoxical role in medicine for over 70 years. Initially developed in the 1930s and widely adopted after World War II, it became a cornerstone of global malaria prophylaxis and treatment due to its high efficacy, low cost, and convenient dosing. However, its dominance was curtailed by the inexorable spread of parasite resistance, which has rendered it largely ineffective against the most lethal malaria parasite, Plasmodium falciparum, in most parts of the world. Serendipitous clinical observations during its widespread use led to its repurposing as a disease-modifying antirheumatic drug (DMARD). Today, its most significant clinical applications are in the management of autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), where it exerts immunomodulatory effects by interfering with antigen presentation and inflammatory signaling. This therapeutic utility is tempered by a significant safety profile, characterized by the risk of irreversible retinopathy and potentially fatal cardiotoxicity, particularly with the long-term, high-dose regimens required for autoimmune diseases. The recent, intense but ultimately unsuccessful investigation of Chloroquine for the treatment of COVID-19 served as a modern case study in the complexities of drug repurposing, underscoring the critical need for rigorous clinical evidence to validate preclinical hypotheses. This report provides a comprehensive monograph on Chloroquine, detailing its chemical properties, pharmacological mechanisms, clinical applications, and complex safety considerations.

Chemical Identity and Pharmaceutical Profile

A thorough understanding of Chloroquine's pharmacological behavior begins with its fundamental chemical and physical characteristics.