Effects of intracarotid admimistration of GABA and its related compounds on the perfused cat brain

ネコ脳灌流法を用いて頸動脈系に一定条件下でGABAおよびその関連物質を注入し,脳波,脳血流量,体側血圧に及ぼす作用を調べ,各物質の作用力価を比較した.被検物質はGABA, β-ヒドロキシーGABA, β-フェニール-GABA, γ-ヒドロキ酪酸, γ-ヒドロキシ-β-アミノ酪酸, γ-アミノブチリルコリン, ホモカルノシン, カルノシン, γ-グアニジノ酪酸である.脳波変化をきたすものでは,その変化はいずれも徐波群発などの抑制作用を示した.脳波抑制作用を示したものにGABA, BH-GABA, BP-GABA, GH-BA, Carnosineがある.このうちGABAの作用が最も弱く,BH-GABA, Carnosineがこれに続ぎ,GHBAとBP-GABAが最も強い作用を示した.Homocarnosine硫酸塩とGGBA塩酸塩では逆に発作発射をきたしたが,これは塩の作用と考えられる.脳血流量の変化をきたす場合には,いずれも流量増大の傾向を示した.脳血流量増大作用を示したものにBH-GABA, BP-GABA, GHBA, Carnosineがあるが,このうちBP-GABA, GHBA, Carnosineが著明であつた.体側血圧の変化をきたす場合には,いずれも降圧的に作用した.降圧作用を示したものにGABA, GABA-Ch, Homocarnosine, Carnosine, GGBAがあるが,このうち, GABA, GABA-Chの作用が強かつた.また,GABAで脳波変化をおこす脳血中有効濃度を求めるため,GABAの各投与量に〔u-(14)C-GABA〕を加え,流出脳静脈血中の放射能を回収し,その経過図から脳血中に5mg/ml以上のGABAが存在する時間だけ脳波が抑制されることがわかつた.For the purpose to study the effects of GABA and its related compunds on EEG, cerebral blood flow and systemic blood pressures, GABA and related compounds were administered into the carotid system of perfused cat brains under a certain fixed condition and the intensity of each drug action was compared. The agents in the experiments were GABA (gamma-amino-butyric acid), β-hydroxy-GABA, β-phenyl-GABA, γ-hydroxybutyric acid, γ-hydroxy-β-aminobutyric acid, γ-aminobutyrylcholine, homocarnosine and γ-guanidinobutyric acid. Those agents that induced changes in EEG all shoed inhibitory effects such as slow bursts. Those that had inhitory effect on EEG were GABA, β-hydroxy-GABA, β-phenyl-GABA, γ-hydroxy-butyric acid and carnosine. Among them GABA showed the least effect followed in ascending order by β-hydroxy-GABA, carnosine and γ-hydroxybutyric acid and β-phenyl-GABA being most potent. On the contrary, sulfate salt of homocarnosine and chloride salt of γ-guanidiobutyric acid induced transient excitatory changes, but this seemed to be the effect of salts. In the cases where changes occurred in the cerebral blood flow, there was an increasing tendency of the blood flow in every cases. Those agents that induced the increase in blood flow were β-hydroy-GABA, β-phenyl-GABA, γ-hydroxy-butric acid and carnosine, and of them such an increasing effect was marked with β-phenyl-GABA, γ-hydroxybutyric acid and carnosine. In the cases where changes were brought on the systemic blood pressures, the effect proved to be depressing in every case. The agents showing such a depressing effect were GABA, γ-aminobutyrylcholine, homocarnosine, carnosine and γ-guanidino-butyric acid. Of them the effects of GABA and γ-aminobutyrylcholine proved to be strongest

Effects of intracarotid administratraion of glutamic acid and its related compounds on the perfused cat brain

By means of brain perfusion method, for the purpose to study the effects of glutamic acid and its related amino acids on EEG, cerebral blood flow and systemic blood pressures, these amino acids were administered into the carotid system of perfused cat brains under a certain fixed condition and the intensity of each drug action was compared. The amino acids tested in the experiments were L-glutamic acid, L-aspartic acid, N-methyl-D-aspartic acid, N-acetyl-DL-aspartic acid, β-hydroxy-glutamic acid, L-glutamic acid-Na, L-aspartic acid-Na, and N-acetyl-DL-aspartic acid-Ca. For EEG, acidic amino acids induce transient excitatory changes followed by inhibition. These excitatory changes prove to be low-amplitude fast waves or burst of seizures, and postexcitatory inhibition to be slow waves or flat waves. N-methyl-D-aspartic acid, even in a minimal dose, induces marked bursts of seizures followed by L-glutamic acid, L-aspartic acid, L-glutamic acid-Na, and L-aspartic acid-Na, in their potency. Generally, N-acetyl-DL-aspartic acids show only low-amplitude fast waves but some of them do induce burst of seizures. β-Hydroxy-glutamic acid elicits only low-amplitude fast waves but never burst of seizures. N-Acetyl-DL-aspartic acid-Ca, differing from the free form, never induces excitatory changes. For the cerebral blood flow, acidic amino acids decrease the blood flow, but those that show a strong decreasing effect are N-alkyl amino acids such as N-methyl-D-aspartic acid and N-acetyl-DL-aspartic acid. On the Other hand, acidic amino acids increase the systemic blood pressure, and of them such an effect is especially marked with N-alkyl amino acid