Intracerebral distribution pattern of radioactive morphine and morphine-like drugs after intraventricular and intrathecal injection

Summary The intracerebral distribution patterns of ¹⁴C-morphine, ³H-dihydromorphine, and ³H-fentanyl after intraventricular injection were studied autoradiographically in rats and rabbits. The extent of permeation into the ventricular wall was measured at different times after injection. The hydrophilic morphine and dihydromorphine could be demonstrated within the tissue up to 4 hours. They seemed to be retained within the gray matter and hindered in crossing fiber bundles. On the other hand, the lipophilic fentanyl was quickly removed from the brain but remained relatively longer demonstrable within the white matter. Also, after intrathecal injection of ¹⁴C-morphine a time dependent spread from the injection site was observed. The use of autoradiography in pharmacological experiments as described was found advantageous. Thus, it is possible to correlate directly, the time course of the pharmacological effect and the respective distribution pattern of the drug applied. This may lead to better information about the probable sites of drug action.     

An Ion Displacement Membrane Model

The usual assumption in treating the diffusion of ions in an electric field has been that the movement of each ion is independent of the movement of the others. The resulting equation for diffusion by a succession of spontaneous jumps has been well stated by Parlin and Eyring. This paper will consider one simple case in which a different assumption is reasonable. Diffusion of monovalent positive ions is considered as a series of jumps from one fixed negative site to another. The sites are assumed to be full (electrical neutrality). Interaction occurs by the displacement of one ion by another. An ion leaves a site if and only if another ion, not necessarily of the same species, attempts to occupy the same site. Flux ratios and net fluxes are given as functions of the electrical potential, concentration ratios, and number of sites encountered in crossing the membrane. Quantitative comparisons with observations of Hodgkin and Keynes are presented.     

Non-Newtonian Behavior of Blood in Oscillatory Flow

Sinusoidal oscillatory flow of blood and of aqueous glycerol solutions was produced in rigid cylindrical tubes. For aqueous glycerol, the amplitude of the measured pressure gradient wave form conformed closely to that predicted by Womersley's theory of oscillatory flow, up to Reynolds numbers approaching 2000. Blood differed significantly from aqueous glycerol solutions of comparable viscosity, especially at low frequencies and high hematocrits. As frequency increased, the hydraulic impedance of blood decreased to a minimum at a frequency of about 1-2 CPS, increasing monotonically at higher frequencies. The dynamic apparent viscosity of blood, calculated from Womersley's theory, decreased with increasing flow amplitude. The reactive component of the hydraulic impedance increased with frequency as predicted by theory; the resistive component decreased with increasing frequency, differing from the resistance of a Newtonian fluid which increased with frequency.