Membrane expansion of the erythrocyte by both the neutral and ionized forms of chloropromazine

Abstract 1. 1. A charged form of chlorpromazine, chlorpromazine methochloride, protected erythrocytes from hypotonic hemolysis. It had about 1/75th the potency of chlorpromizine HCl. 2. 2. The anti-hemolytic effect of chlorpromazine·HCl was potentiated at higher pH's when erythrocytes, originally suspended in pH 7, were hypotonically hemolyzed in solutions of different extracellular pH's. In these experiments the pH was different on each side of the membrane. 3. 3. No such pH dependency of chlorpromazine potency was seen when the pH was the same on both sides of the membrane. Intact cells were hemolyzed in hypotonic solutions of different pH. A Coulter counter and computer was used for measurng the mean cell volume of these fresh erythrocyte ghosts. The intracelular pH of the spherical ghosts was assumed to be equal to the extracellular pH. It was found that chlorpromazine·HCl increased the ghost mean cell volume to about the same extent over the pH range 5.9–9.8 5·10 −6 M chlorpromazine·HCl increased the mean cell volume by 5.2 μ 3 and the membrane area by about 3.2 μ 2 over a wide pH range. 4. 4. It is concluded that both the free base and the charged form of chlorpromazine contributed to its membrane action of expanson and anesthesia; both forms of the drug apparently expand the erythrocyte membrane by about an equal amount. 5. 5. It is concluded that the charged form of chlorpromazine affects the erythrocyte membrane from both the internal and external aspects of the membrane. This is identical to the situation which obtains in nerve fibers where both sides of the membrane are sensitive to quaternary anesthetics.