The Membrane Binding of Morphine, Diphenylhydantoin, and Tetrahydrocannabinol

Abstract

The adsorption of morphine to guinea pig brain synaptosome membranes and to human erythrocyte membranes was found to be passive, and unaffected by time, temperature, ouabain, dinitrophenol, saponin, or ATP. The membrane/buffer partition coefficient for morphine was 35 (at low ionic strength) and 1.2 (at high ionic strength). The synaptosome membrane/buffer partition coefficient for diphenylhydantoin was around 60 (at pH 8), while that for Δ⁹-tetrahydrocannabinol (THC) was around 380 (in the concentration range of around 10⁻⁵ M). The partition coefficient for the latter drug dropped by a factor of two or three with increasing drug concentrations for both erythrocyte ghosts and synaptosomes; there may be two types of binding sites for THC. The minimum blocking concentrations (frog sciatic nerve) were 1.1 × 10⁻² M for morphine, and 8.3 × 10⁻⁴ M for diphenylhydantoin. The anesthetizing membrane concentrations of these two drugs are close to the value predicted by the Meyer–Overton rule for local anesthesia (30 mmol/kg dry membrane).