Delayed evacuatory function due to specific smooth muscle reactivity in the gastrointestinal tracts of tacrine-treated rats.

Most of the side effects induced by tacrine are associated with the gastrointestinal (GI) tract. The aim of the study was to analyze the nature of radiographically registered, tacrine-induced changes in evacuatory function, as well as to find a possible correlation with the immediate in vitro action of the drug on smooth muscles from the GI tracts of rats. The tacrine dose we used reliably delayed GI passage: contrast matter was not fully evacuated, predominantly from the stomach and cecum. The delay resulted from changes in tone and peristaltic activity, specific for the various regions of the tract. These changes were associated with a superposing of the responses due to the anticholinesterase and noncholinergic action of tacrine.

Influence of tacrine on dopamine-induced reactions of the gastric smooth muscle of rats.

The clinical usage of the cholinesterase inhibitor tacrine for treatment of Alzheimer's disease is accompanied by adverse effects on the gastrointestinal tract. These adverse effects are a result of the direct action of tacrine on the intestinal smooth muscles or of the modulation of certain neurotransmitters regulating gastrointestinal functions. Dopamine is a neurotransmitter that modulates gastrointestinal motility. This study was designed to examine in vitro the effects of tacrine on dopamine-induced changes in spontaneous activity of smooth muscle preparations from rat's gastric corpus. The mechanical activity was isometrically registered. Tacrine 1.10(-7)-1.10(-5) mol/l caused smooth muscle contraction, which was blocked by atropine 1.10(-6) mol/l. Tacrine 1.10(-4) mol/l provoked a relaxation resistant to atropine. Dopamine and D(2)-receptor antagonists haloperidol and R121 had no effect on tacrine-induced relaxation. Dopamine-induced contraction was concentration-dependent. It was blocked by D(2)-receptor antagonists haloperidol and R121 and by tacrine 1.10(-4) mol/l. In the presence of tacrine 1.10(-7)-10(-5) mol/l or atropine the dopamine-induced contraction was significant. The data obtained suggested that tacrine 1.10(-4) mol/l inhibited the dopamine effects on gastric corpus smooth muscles. The effect was probably not dependent on its anticholinesterase activity or not realized through direct influence on D(2)-dopamine receptors.

Effects of phenobarbital, carbamazepine and a combination of both on corazol-induced changes in the bioelectric activity of rat brains.

Combined forms of epileptic seizures are known to require combinations of antiepileptic drugs for their management. This study investigated the effects of such a combination consisting of phenobarbital and carbamazepine (mixed in the 1:4 ratio) as well as the effects of each component used separately on the Corazol-induced bioelectrical brain discharges. The effects were studied in a group of rats that received only a single dose of the drugs, as well as in a group that underwent 14-day anticonvulsant treatments. The bioelectric activity of the brain was recorded using an EEG method. In a single dosage, the combination of phenobarbital and carbamazepine was found to be more effective than its components. The decrease of Corazol-induced discharges was more pronounced in a single administration of the combination than when it was applied repeatedly. Development of a cumulative effect was observed in respect to carbamazepine action on the Corazol-induced discharges.

[A pharmacological analysis of the mechanism of action of ethosuximide]. / Farmakologicheskii analiz mekhanizma deistviia étosuksimida.

Ethosuximide is one of the means of treatment of minor epilepsy but hardly any data on its mechanism of action are available in the literature. Anticonvulsant agents are known to bring about changes in the functions and in the interaction between some of the mediator systems within the central nervous system. An assessment of the status of neuromediator systems can be made on the basis of the response of isolated smooth muscle strips to the action of agonists and antagonists of various receptors. It was found by the pharmacological analysis of isolated strips from the rat stomach (antrum and corpus strips), the seminal duct and the cervical vein that ethosuximide induces a reduction in the physical contractile activity and the tone of smooth muscle preparations. Smooth muscle relaxation caused by ethosuximide is not blocked by different receptor inhibitors such as dihydroergotamine, propranolol, atropine, chlorpromazine, haloperidod and indomethacin. Ethosuximide causes a significant reduction in the physical contraction of smooth muscles produced by potassium chloride depolarization, with a stronger impact on the subsequent tonic contraction caused by calcium ions. A reduction in the potassium content of the solution has no effect on the nature of the action of ethosutimide. It is thus assumed that the probable mechanism of action of ethosuximide consists in lowering calcium transport since the inhibitors of calcium transport sodium nitroprusside and verapamil intensify the blocking effect of ethosuximide on smooth muscle contractile activity.

On octanoic acid-induced hyperventilation--implications for hepatic encephalopathy and Reye's syndrome.

Medium chain fatty acid sodium octanoate was infused into rabbits as a 0.2 M solution over 4 h resulting in blood and brain octanoate levels of 200-800 mumol/l. The infused animals developed marked hyperventilation leading to a mild respiratory alkalosis. Additionally, octanoate infusion brought about hyperammonemia and hyperlactate acidemia. Another group of rabbits also infused with octanoate but pretreated with indomethacin (10 mg/kg b.wt.) developed neither hyperventilation nor hyperammonemia. Therefore, the conclusion made was that octanoate causes the above mentioned disorders through stimulation of prostaglandin synthesis and especially the PGE2 synthesis. Patients with hepatic encephalopathy and Reye's syndrome have elevated levels of plasma octanoate. The present study suggests that octanoate might be the cause for both the hyperventilation and hyperammonemia observed in patients with hepatic encephalopathy and Reye's syndrome.

[Effect of insulin on the amount of somatotropic hormone, immunoreactive insulin, blood sugar and free fatty acids in sheep]. / Vliianie na insulina vurkhu kolichestvoto na somatotorpniia khormon, imunoreaktivniia insulin, kruvnata zakhar i svobodnite mastni kiselini priovtse.

Studied was the effect of the venous injecting of insulin at the rate of 0.2 IU/kg body weight on the changes in the amount of the somatotropic hormone (STH), the immunoresponsive insulin, the free fatty acids (FFA), and the blood sugar in the serum of sheep, following their dynamics up to the 150th minute after application. The STH level rose to its peak value at the 60th min., after which it showed a lowering trend. The level of FFA dropped sharply after the injection of insulin, its lowest value being registered at the 60th min., after which it rose. By the end of the experiment the blood values of STH and FFA were close to those of the control animals. The blood sugar level started to drop 30 min. following the injection of insulin, and up to the end of the experiment a hypoglycaemic reaction was observed.