Procarbazine (DB01168): A Comprehensive Pharmacological and Clinical Monograph

Introduction and Overview

Procarbazine is a potent antineoplastic agent belonging to the methylhydrazine class of drugs.[1] It functions as a cell cycle phase-nonspecific prodrug that, following metabolic activation, exerts its primary cytotoxic effects as a DNA alkylating agent.[3] Historically, Procarbazine holds a landmark position in the field of oncology. It was an integral component of the MOPP (mechlorethamine, Oncovin® [vincristine], procarbazine, prednisone) regimen, which in the 1960s became one of the first combination chemotherapy protocols to demonstrate the potential to cure a disseminated cancer—advanced-stage Hodgkin's disease.[3] This breakthrough established a new paradigm in cancer treatment, proving that systemic, metastatic malignancies could be effectively eradicated with combination drug therapy.

The pharmacological profile of Procarbazine is uniquely complex, a direct consequence of its developmental origins. The drug was not initially designed as a cancer therapeutic but emerged from a research program screening hydrazine derivatives for monoamine oxidase (MAO) inhibitory activity.[8] Its antineoplastic properties were discovered serendipitously during this process. This dual heritage—a potent cytotoxic agent fused with a neurologically active MAO inhibitor—is the central characteristic that defines its clinical use and its significant safety concerns. The residual MAO inhibitory activity is not a minor off-target effect but a core feature that dictates a stringent set of dietary and drug-related precautions to prevent potentially fatal interactions.[2]