シリコンゴム膜を介しての各種薬剤の透過および脳内拡散に関する実験的研究—in vivo study

EXPERIMENTAL STUDIES OF PERMEABILITY AND INTRACEREBRAL DIFFUSION OF VARIOUS NEUROTROPIC DRUGS THROUGH THE SILASTIC MEMBRANE

I．はじめに

　シリコンゴム膜が各種薬剤を透過させることは1964年Forkmann and Long^2）の報告以来知られている。シリコンゴム膜のこのような特徴を生かし，その脳内埋め込みにより脳内薬理作用の解明，神経生理学，さらには行動異常てんかん，痛みなどの定位脳手術的薬物療法への応用が考えられてきている。一方現在までシリコンゴム膜を透過することが知られている薬剤のうちlido—caine,l-dopa,l-norepinephrine,serotonineの4種の薬剤は神経薬理学および神経生理学上重要である。しかしながらこの4種の薬剤を用いてシリコンゴム膜脳内埋め込みを神経生理の解明さらには臨床に応用するにはこの4薬剤の膜透過後の薬剤の脳組織での拡散状態を知つておく必要がある。したがつてシリコンゴム膜脳内埋め込みを介しての4薬剤の脳内拡散状態を未だ報告をみないオートラジオグラフィーを実験手技として検討したので報告する。

Continuous topical applications of neurotropic drugs to the restricted area of the central nervous system are often reqired in the field of stereotaxic neurosurgery. So since it is neccessary to know the extent of diffusion of neurotropic drugs, attempts were made to visualize the intracerebral diffusion of 1-dopa, 1-norepinephrine, serotonine and lidocaine through a chemode.

An in vivo chemode was embedded in the capsula interna and caudate necleus of adults cats and the state of the intracerebral diffusion of above drugs was investigated by autoradiography and the following results were obtained.

1. Autoradiography revealed that accumulations of silver grains were rather restricted around the chemode approximately 0.1-0.3 mm, in distance from the margin of chemode to the appreciable outer margin of silver grain. Accumulations of silver grains were about the same in cases of chemode implantation into the caudate as that into the internal capsule, indicating that there is no regonal difference in the mode of diffusion of these drugs particularly between the gray and white matters. Each drug showed the maximal diffusion at 1 hour-1 hour 30 min. The time of maintenance of maximal diffusion range was 3 hours for serotonine and lidocaine, 1 hour 30 min. for 1-dopa and in the case of 1-norepinephrine the time was up to one hour.

2. It was shown that a fluctuation of the intra-cerebral diffusion was clearly influenced by the variations of concentration of the drug in intra-cerebral chemode. Further, within the chemode even in the case of continuous administration of the drug as a result of which a constant amount for a long duration is maintained, the intracerebral diffusion range is limited and does not excess the diffusion range of that of a single administration.

Via a chemode implanted in the Edinger-Westphal nucleus, the time course change of the diameter of pupils by lidocaine administration coincided with the autoradiography findings.