Mechanism of the inhibitory effect of histamine on amygdaloid-kindled seizures in rats

PURPOSE: The mechanism of the inhibitory effect of histamine on amygdaloid-kindled seizures was investigated in rats. METHODS: Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. A guide cannula made of stainless steel tubing was implanted into the right lateral ventricle. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. EEG was recorded with an electroencephalograph; stimulation of the amygdala was applied bipolarly every day by a constant-current stimulator and continued until a generalized convulsion was obtained. RESULTS: Intracerebroventricular (i.c.v.) injection of histamine at doses of 2-10 microg resulted in a dose-related inhibition of amygdaloid-kindled seizures. I.c.v. injection of calcium chloride at doses of 10-50 microg and A23187 at doses of 2-10 microg also caused dose-dependent inhibition of amygdaloid-kindled seizures. Calcium chloride at a dose of 10 microg, which showed no significant effect on amygdaloid-kindled seizures when used alone, significantly potentiated the effect of histamine. Similar findings were observed with A23187 at a dose of 2 microg. In addition, EGTA and EGTA/AM antagonized the inhibition of kindled seizures induced by histamine. Moreover, the inhibition of kindled seizures induced by histamine was antagonized by KN62. However, calphostin C did not antagonize the inhibitory effect of histamine. CONCLUSIONS: These results indicated that histamine-induced inhibition of amygdaloid-kindled seizures may be closely associated with a calcium calmodulin-dependent protein kinase II activation pathway.     

Differential Sensitivity to the Effects of Psychotropic Drugs: Psychotics vs Normals; Asian vs Western Populations

Abstract: The effects and side-effects of psychotropic drugs are determined by many variables, and the host factor is one of the most important. A lower sensitivity of schizophrenics than normals to the sedative effect of chlorpro-mazine and of manic depressives to imipramine were demonstrated quantitatively by a higher percent time of waking EEG following medication. The mean therapeutic dose of chlorpromazine for the manic state was found to be much lower in Japanese than in Western populations in a controlled study comparing the antimanic efficacy of carbamazepine and chlorpromazine. A lower therapeutic dose in Asian populations has been reported also on other antipsychotic drugs, lithium, and tricyclic antidepressants. The lower therapeutic dose level was discussed from the standpoint of transcultural psy-chopharmacology.     

Anti-Manic and Prophylactic Effects of Carbamazepine (Tegretol) on Manic Depressive Psychosis A Preliminary Report

• 1). The anti-manic, anti-depressive and prophylactic effects of carbamazepine (CAZP, Tegretol-Ciba Geigy) on the endogenous mani-depressive psychosis (MDP) were investigated on 50 MDP cases. The dosage of the drug ranged from 200 to 1,200 mg daily (usually 400 to 600 mg).
• 2). The effect of CAZP on 33 manic states was: “markedly effective” seven (23%), “effective” six (19%), “slightly effective” five (16%), “ineffective” 13 (42%), whereas the effect on six depressive states was: “markedly effective” one and “ineffective” five. No definite relationship was found between the kinds of drugs in combination use and the effect of CAZP. No significant difference of the CAZP effect was found in the four patient groups with different age of onset of the illness, nor among the “continuous,”“frequent” and “periodic” type cases.
• 3). The prophylactic effect of CAZP on 27 cases in which the assessment of the effect on the manic episode was possible was: “markedly effective” 13 (48%), “effective” seven (26%) and “ineffective” seven (26%), whereas that for depressive episode was: 12 (45%), two (7%) and 13 (48%), and the result of the general assessment on each patient was 14 (43%), 10 (30%) and nine (27%), respectively. The kinds of drugs in combination use, age of onset and type of course of the illness did not have any influence on the prophylactic effect of CAZP.
• 4). The prophylactic effect on MDP of CAZP did not parallel that of lithium salt, but CAZP may be effective on cases which did not respond to lithium and vice versa.
• 5). Side-effects such as ataxia, dizziness, exanthema, drowsiness and headache were observed in five of the cases, and the CAZP was discontinued in four of them.
• 6). The mechanism of effectiveness of the CAZP on MDP was discussed.