Evaluation of Local Anaesthetics

Introduction

• Definition — Local anaesthetics (LAs) reversibly block generation and conduction of the nerve impulse, producing loss of sensation (especially pain) in a restricted area without structural nerve damage.
• What evaluation means — Evaluation (screening) of LAs is the battery of validated in vitro and in vivo preclinical methods used to detect, quantify and rank a candidate's local-anaesthetic activity relative to a reference (standard) LA, and to characterise its safety — a special application of comparative bioassay.
• Why a panel of models — An LA is used clinically by several distinct routes — surface (topical), infiltration, conduction (nerve) block, spinal and epidural — and a molecule may excel in one mode yet be useless in another (e.g. procaine is a good injectable but a poor surface agent; benzocaine/oxethazaine are topical-only). No single assay captures all uses, so screening uses a tiered panel mapped to the clinical routes.
• Core endpoints — Every LA-evaluation answers the same questions: does it produce anaesthesia (efficacy), how potent is it vs the standard, how fast is the onset (latency), how long is the duration, is the block reversible, and what is its toxicity (local + systemic) and vasoactivity.
• Reference drugs — Benchmarks are chosen by route — surface: lidocaine, tetracaine, proparacaine, cocaine (historical control); infiltration / nerve block: lidocaine (workhorse standard, relative potency 1), procaine (low-potency standard), bupivacaine (long-acting, potency 4–5), ropivacaine (potency 3–4); spinal: lidocaine, bupivacaine, ropivacaine.