Relationship between the passage of local anaesthetics across the blood-brain barrier and their effects on the central nervous system.

The transfer of procaine and lignocaine from blood to cerebrospinal fluid (c.si.) was studied in six patients and in twelve dogs. Local anaesthetics appeared very rapidly in the c.s.f. after intravenous administration. Within 20 minutes, a c.s.f./plasma ultrafiltrate ratio around 0.9 was reached. Para-aminobenzoic acid, a procaine metabolite, appeared in c.si. later than procaine. This is explained by a different rate of drug entry into the c.s.f. and by the need for previous procaine splitting by plasma cholinesterase. The rapid transfer of local anaesthetics corresponds with their high lipidsolubility and low degree of ionic dissociation at the pH of the body. The free movement of drugs to and from the brain accounts for the controllability of general anaesthesia induced by the intravenous administration of local anaesthetics.