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Many antibiotics have been developed and used for the treatment of infectious diseases. Although they have been known to have various adverse effects, most of the mechanisms remain still unknown. New quinolones are well known to induce convulsions and their convulsant activity enhanced by concurrent administration of anti-inflammatory drugs. Each new quinolone has an individual convulsant activity with individual drug-interaction with anti-inflammatory drugs. And enoxacin, lomefloxacin and gatifloxacin have been reported to decrease blood glucose levels in a dose-depend- ent manner, but ciprofloxacin and levofloxacin had no effect on the levels. It should be important to know the safety profile of antimicrobial agents before doctors administer these agents to the patients with infectious diseases.

Ro 5-4864, a specific agonist of the peripheral-type benzodiazepine receptor (PBR), elicited convulsions 2.6 times more potently in EL mice (an animal model of epilepsy) than in DDY mice (control animal). A binding assay revealed a 50% higher density of [3H] Ro 5-4864 binding sites in the mitochondrial fraction (i.e., mitochondrial benzodiazepine receptors; MBR) of the brain tissues in EL mice as compared with DDY mice. On an elevated plus-maze, EL mice showed fear responses similar to those increased in DDY mice after PBR stimulation, suggesting a hyperfunction of MBR underlying the abnormal behaviors of EL mice. In fluorometric studies using NG108-15 cells, Ro 5-4864 depolarized mitochondrial membranes and, possibly as a consequence of this, raised intracellular Ca2+. Finally, we propose that MBR could be a major target of therapy for various neurological disorders, so drugs such as "mitochondrial membrane stabilizers" should be developed.

Quisqualic acid (QA) is a potent neuroexcitant and a heterocyclic analogue of glutamate as is kainic acid. Twenty micrograms of QA in unilateral lateral amygdaloid nucleus of cats produced a transient limbic status epilepticus lasting 20-30 hours. Over 14 days after recovery from the limbic status, the animals received daily electrical stimulation to the ipsilateral hippocampus at the intensity of afterdischarge threshold which was determined before the injection of QA. These stimulations resulted in secondarily generalized convulsive seizures in all animals within 4 to 12 days. Spontaneous secondarily generalized seizures were confirmed in two cats after completion of the hippocampal kindling. This rapid completion of the kindling process is interesting phenomenon in contrast to the report that the hippocampal kindling took nearly 60 days. This rapid completion of the kindling effect is considered to be due to the transfer effect (Goddard, 1975) established in the ipsilateral hippocampus by severe bombardments from the amygdala stimulated by the injection of QA as the primary focus. In addition, the pathological changes in the amygdala and hippocampus on the injected side might be related to the rapid kindling process of the ipsilateral hippocampus as the irritable foci.

Because of its putative long-acting cholinomimetic property, phosphatidylcholine (Pc, lecithin), is expected to have a therapeutic efficacy on states in which a cholinergic hypofunction in the CNS is pathognomonic. Cholinomimetic drugs in general have been reported to enhance proconvulsive predisposition of animals in various experimental situations. In our experiments, however, neither incidences of spontaneous myoclonic jerks nor pentylenetetrazol (Ptz)-induced seizure was changed in Mongolian gerbils, 12 hr after 95% soybean Pc (755 mg/kg) pretreatment. The ED50's of Ptz in inducing tonic-clonic convulsion were 44.0 mg/kg for control group which was pretreated with vehicle alone and 42.3 mg/kg for Pc-pretreated group. Some recent observations on humans and animals pose a question concerning Pc's action through the central cholinergic transmission. These and our results indicate that further investigations using behavioral parameters of animals are necessary before establishing and characterizing the central action of Pc.

Coptis root is frequently utilized as a sedative in Chinese medicines, however, the central depressant action of this compound has not been reported. Such being the case, the central depressant actions of methanol extract of coptis root, its active ingredients such as non-alkaloids fraction, tertiary base fraction, quarternary base fraction, magnoflorine fraction, berberine hydrochloride, coptisine hydrochloride and the extract from SAN O SHA SHIN TO being one of the preparations which contain coptis root were investigated in mice. The antigastric ulcer action of these substances was also examined in rats. All substances were given orally. Sontaneous movement and coordinative motor activity were not depressed by methanol extract, non-alkaloid fraction quarternary base fraction, magnoflorine fraction, berberine hydrochloride, coptisine hhdrochloride and the extract from SAN O SHA SHIN TO. There was no inhibition of chemical- and electro-shock-induced convulsion, morphine induced Straub's tail reaction, apomorphine-induced masticating motion and aggressive behavior induced by electrical stimulation. A loss of righting reflex due to hypnotics was not potentiated by the substances. The quarternary base fraction did not elicit central depression, while the tertiary base fraction slightly depressed the function of the central nervous system. Quarternary base alkaloids such as berberine exerted a slight antiulcer effect.

The present study was designed to investigate the proconvulsant effect of morphine (10, 30, 50 mg/kg, sc) in mice on pentylenetetrazol (PTZ)-, picrotoxin-, and bicuculline (BCC)-induced convulsions which are thought to be produced by interactions with GABAergic systems. Morphine increased the severity of seizures induced by the ip (50 mg/kg) and sc (90 mg/kg) routes of administration of PTZ. An administration of morphine caused an increased incidence of multiple seizures following both ip and sc administration of PTZ and prolonged the latency to onset of seizures induced by ip injection of PTZ. Repeated morphine administration (30, 50 mg/kg, ip x 4d) also caused an increased incidence of multiple seizures and the latency to onset of seizures by ip injection of PTZ. All these effects of morphine are naloxone-sensitive. Single morphine administration potentiated seizures induced by picrotoxin (2 mg/kg, iv) and BCC (20 mg/kg, iv). These results demonstrate that morphine has a proconvulsant effect on PTZ-induced seizures in the mouse.

Since propiverine hydrochloride (P-4), an anti-pollakiuria drug, increased the spontaneous motor activity of mice in general pharmacological experiments, behavioral pharmacological effects of P-4 were further studied by experiments for spontaneous motor activity, convulsion-inducing effect, and differential reinforcement of low rate (DRL) schedule in mice and rats. A high dose of P-4 (100 mg/kg, p.o.) increased slightly but significantly the spontaneous motor activity level in rats. P-4 (10, 20, and 50 mg/kg, p.o. for one week) did not affect the activity level in mice, whereas methamphetamine caused the reverse tolerance after being daily administered for one week at a dose of 1 mg/kg, s.c. P-4 (20, 50, and 100 mg/kg, p.o.) did not induce convulsive behaviors such as minimal full seisure (M.F.S.), clonic convulsion (C.C.) and tonic convulsion (T.C.) in combination with a dose (40 mg/kg, i.p.) of pentylenetetrazol, which is below the threshold in mice, whereas methamphetamine (8 mg/kg, s.c.) in combination with pentylenetetrazol induced M.F.S. Under a DRL schedule for food reinforcement in rats, P-4 (50 and 100 mg/kg, p.o.) lowered the reinforcement rate, but it did not affect other parameters. On the other hand, methamphetamine (0.5, 1, and 2 mg/kg, s.c.) facilitated DRL responses and lowered the reinforcement rate, mean of inter-response time, efficiency, respectively, in a dose-dependent manner. These results suggest that P-4 does not possess the methamphetamine-like CNS stimulating effect.