クロールプロマジンの脳代謝に及ぼす影響についで

Studies on the Effect of Chlorpromazine on Cat's Brain Cortex

緒言

　クロールプロマジン（以下CPと略）は，1946年仏国で合成され，ラボリー博士が之を人工冬眠に利用して外科手術に新分野を拓いて以来，医学の各領域に広く用いられる様になつた。CPはTranquilizerとして間脳中枢に働くといわれているが，CPの普及に伴いその作用機序に関して各方面から研究されている。Salzman及びBrodie^1）によると，犬にCPを投与したとき，脳及び肺にCPが最も多く発見されるという。Federov^2）は，CPは血液脳関門を容易に通過するといつている。又Wase^3）等はS³⁵-CPを用いて実験し，これが視床下部に最も多く，次いで大脳は皮質に多く集ることを報告している。一方Federov^2）は大脳皮質にCPが高濃度に集ると報告している。何れにしても薬理学的侵襲部と考えられる脳幹及び大脳にCPが強い親和性を有するということは興味深いことである。

　吾々は，CPの脳波に及ぼす影響を観察すると共に，CPに強い親和性を示すといわれる大脳皮質の生化学的変化について脳代謝の面より追究した。

　The Purpose of this work is to observe the effect on brain metabolism of chlorpromazine whichnow utilizes in many fields of medicine. Cats, weighing 2 to 3 Kg were used for the experiment. Result is following.

　(1) In cats, narcotized with ether, the anterior part of the skull was removed over an area of about2cm² on each side and a cannula was insertedin the femoral vein. Then after injection subcutanously of curale, animal was set to continueartificial respiration.

　After freezing of one side of cortex, chlorpromazine (10mg/kg) was injected intravenouslythrough the cannula and few minutes later theother cortex was frozen.

　Frozen materials were separated into three fractions e. g. acid soluble, lipid and nucleic acidfraction according to Schneider's method. In eachfraction total nitrogen, amino nitrogen and inorganic phosphorus were determined in homogenatedirectly. Electrocorticogram shows to be produceda depressive or sleeping pattern by chlorpromazineadministration. Biochemically, it presents that chlorpromazine produce a decrease of acid solubletotal nitrogen and an increase of acid solubleamino nitrogen and total nitrogen, amino nitrogenand inorganic phosphorus in nucleic acid fraction.Glucose and lactic acid content show no significantdifference between before and after administrationof chlorpromazine. Obtained result suggests thatchlorpromazine may produce a depression of brainmetabolism and an accumulation of energy richcompounds such as nucleic acid in cortex.

　(2) In cats, narcortized with phenobarbital, theoperation was as the same as the former groupwithout the injection of curale and setting toartificial respiration. Freezing and analysis ofcortex were prepared as well as the first group. In this group, electrocorticogram presents no siggnificant difference by the administration of chlorpromatine (10mg/kg).

　Biochemical changes in cortex produced bychlorpromazine injection were as follows; an increase of acid soluble total nitrogen, aminonitrogen, lactic acid and nucleic acid inorganicphosphorus and a decrease of glucose. In an administration of chlorpromazine under phenobarbitalnarcosis, obtained results suggest some intoxication effect on cortex at the same time a depressionof brain metabolism.