Effect of sparteine on status epilepticus induced in rats by pentylenetetrazole, pilocarpine and kainic acid.

The long-term effects of status epilepticus (SE) include severe clinical conditions that result in disorders of various organs and systems as well as neurological damage that could lead to death. Sparteine is a quinolizidine alkaloid synthesized from most Lupine species, and its anticonvulsive effect was evaluated in the pentylenetetrazole model of SE. However, efforts to clearly determine the anticonvulsive effect of sparteine have not been made previously. For this reason, we consider it important to study the anticonvulsant effects of sparteine at the level of behavior and EEG activity in three different SE models. The animals of the control groups, which received intraperitoneal pentylenetetrazole (90 mg/kg), kainic acid (9 mg/kg) or pilocarpine (370 mg/kg), exhibited convulsive behavior and epileptiform activity. After sparteine pretreatment (13 mg/kg, administered 30 min before the convulsive drug), the animals administered pentylenetetrazole and pilocarpine exhibited reduced mortality rates compared with the corresponding control groups, while the animals administered kainic acid exhibited a delayed onset of convulsive behavior and decreased seizure duration compared with the corresponding control group. In the three models of SE, a significant reduction in the amplitude and frequency of discharge trains was observed. These results support the anticonvulsant effect of low doses of sparteine and allow us to direct our efforts to other new anticonvulsant strategies for seizure treatment. However, it is necessary to perform more experiments to determine the precise mechanism through which sparteine produces an anticonvulsant effect at this concentration.

Hypoglycaemic effect of quinolizidine alkaloids--lupanine and 2-thionosparteine on non-diabetic and streptozotocin-induced diabetic rats.

The hypoglycaemic effects of two quinolizidine alkaloids: lupanine and 2-thionosparteine were examined in non-diabetic and in streptozotocin-induced diabetic rats. The model of experimental diabetes can be considered to be related to diabetes mellitus type 2 with regards to the impairment of beta-cells' secretory function. A single intraperitoneal injection of 2-thionosparteine at a dose of 8.6 mg/kg lowered the blood glucose levels in diabetic rats at 90 and 120 min after administration and showed similar hypoglycaemic effects to glibenclamide and sparteine, which were used as reference substances. In contrast to glibenclamide, 2-thionosparteine did not result in a significant increase in plasma insulin levels in diabetic rats; an increase was only observed in the non-diabetic group. It was found that lupanine did not exert hypoglycaemic potency in diabetic and in non-diabetic animals and did not significantly increase plasma insulin concentration independent of the group examined. From this study we can state that 2-thionosparteine, but not lupanine, is confirmed to be a possible plasma glucose lowering agent. It is possible that 2-thionosparteine-dependent decrease in blood glucose level is not the only result of this drug's related insulin secretion.

Fallo respiratorio agudo como forma de presentación de una neumonitis por hipersensibilidad al esparto (estipatosis) / Acute respiratory failure presenting as pneumonitis due to esparto hipersensitivity (stipatosis)

Describimos el caso de un paciente con historia de exposición al esparto, que ingresó en la Unidad de Cuidados Intensivos por insuficiencia respiratoria aguda. El reconocimiento temprano de la enfermedad del paciente y la pronta iniciación del tratamiento con corticoides permitieron una buena evolución clínica. El diagnóstico de neumonitis por hipersensibilidad al esparto se sospechó por la anamnesis y el resultado de la biopsia pulmonar, y se confirmó con una prueba de provocación (AU)

Plasma glucose lowering effect of sparteine sulphate infusion in non-insulin dependent (type 2) diabetic subjects.

Sparteine sulphate, given i.v. as a bolus of 15 mg/ml plus 90 mg in 0.9% NaCl 100 ml over 60 min, increases plasma insulin and decreases plasma glucose and adrenaline in non-insulin dependent (Type II) diabetic subjects. The hypoglycaemic effect was also evident in the presence of a high plasma glucose level produced by Biostator changing glucose infusion from 20.2 +/- 2.8 to 26.4 +/- 4.2 mg.kg-1.min-1 (p less than 0.01), and it was potentiated by simultaneous infusion of arginine. No additional effect of sparteine on the peripheral sensitivity to insulin were detected by the euglycaemic, hyperinsulinaemic glucose clamp technique, as the glucose infusion rate (3.1 +/- 0.8 vs 2.6 +/- 1.2 mg.kg-1.min-1) was not statistically significant different in the last 60 min of the experiment. It is concluded that sparteine sulphate enhances beta-cell secretion, causing a fall in the plasma glucose concentration.

[The influence of several membrane stabilizing drugs on the induced hereditary myotonia--a methodic way to test the effectiveness of drugs on myotonia (author's transl)]. / Die Wirkung vershiedener membranstabilisierender Medikamente bei der induzierten und hereditären Myotonie--Darstellung eines methodischen Vorgehens zur medikamentösen Therapieprüfung bei der Myotonie.

The therapeutic effectiveness of several membrane stabilizing drugs was investigated on experimentally induced myotonia by 2,4-Dichlorophenoxyacetate (2,4-D) and in 20 patients with myotonia congenita. Procainamide and quinine showed a better antimyotonic effect in-vitro- as well as in-vivo-experiments on the cold blood muscle and the rat than Sparteine sulfate and Tachmaline (Ajmalin). The two last-mentioned drugs had nearly the same effect. Because of these experimental results only procainamide and sparteine sulfate were clinically used. Quinine was not used because of the well known side-effects. Mention is made of the fact, that the therapeutic effect depends on the dose or the concentration. The results support not only the theoretic considerations on the pathogenesis of myotonia but also recommend to carry out further pharmacological investigations with this method.

[Treatment of arrhythmia in coronary patients and hypertensives with beta blockers and Depasan retard]. / Behandlung von Herzrhythmusstörungen bei Koronarpatienten und Hypertonikern mit Beta-Blockern und Depasan retard.

In the ambulatory of an internal specialist a number of patients suffering from angina pectoris or hypertonia together with arrhythmic troubles received an initial treatment with beta-blockers over a period of 21 days. In cases in which arrhythmia persisted after this initial period the treatment was continued for another 21 days with the addition of Depasan retard in function of a second medicament. This combined treatment in form of an open study was extended to a total number of 50 patients presenting ventricular extrasystolia in 45 cases and in 5 cases absolute arrhythmia in addition to the main disease. Treatment with Depasan retard showed good or satisfactory results in 39 out of 45 patients suffering from ventricular extrasystoles, whilst no effect could be obtained in the 5 cases with absolute arrhythmia. No signs of incompatibility or unwanted interactions were observed in the course of this open study. Based on these results it can be concluded that Depasan retard should be recommended in those cases where on account of persistent arrhythmical troubles and especially extrasystoles, during a treatment with beta-blockers in patients suffering from angina pectoris or hypertonia, and additional treatment with anti-arrhythmical medicaments appears to be indicated.

[Eutergin in the treatment of chronic cerebrovascular disturbance patterns (author's transl)]. / Eutergin in der Behandlung chronischer zerebrovaskulärer Störbilder.

After setting up a catalogue of complaints and signs for the most frequent disturbances of feeling tone of the patients suffering from cerebral arteriosclerosis, consisting of somatically subjective head pain and mental disturbances, treatment was given to 33 patients with cerebrovascular disturbances and 7 patients with similar, although non-vascular, disturbances (4 patients with presenile dementia, 3 patients with tinnitus in otosclerosis), the treatment consisting of eutergin 3 X 1 tablets to 3 X 2 tablets daily, the concomitant cardio-internistic medication remaining the same throughout the treatment course. The type and severity of the symptoms prevailing in each case were determined at the beginning, after 3 weeks and after 6 weeks of the medication with eutergin. It was found that improvement of the somatic-subjective head pain was more pronounced than that of the mental disturbances. Generally speaking, the disturbing somatic or mental signs were those which could be influenced better than the others. As far as the head pain was concerned, the feeling of giddiness, congestion in the head, rapid exhaustion, above all, tinnitus, responded best to the medication (the improvement amounting to approximately 40%), whereas of the mental complaints, a feeling of being "lost" or "abandoned" and a morose mood were most amenable to improvement (degree of improvement approximately 30%). The prevention of the delirogenic effect of antidepressives in senile depression was a remarkable effect; this means that effective antidepressive medication is made possible with the help of eutergin, EEG controls did not reveal any significant effects. There were no side effects. Elevated blood pressure levels showed a tendency to become normal without any dramatic drops. Hence, eutergin is recommended in all kinds of chronic cerebrovascular lesions, provided it is associated with concomitant cardiac and internistic treatment.

[Effect of the administration of Cardiostenol on experimental hepatitis in mice induced with MHV-3 virus]. / Effetto della somministrazione di Cardiostenol sulla epatite sperimentale del topo da virus MHV-3.

Treatment with Cardiostenol (commercial name of a pharmaceutical product containing morphine chloridrate+atropine+sparteine) does not modify the course of hepatitis in mice infected with MHV-3 virus. Similar results were previously obtained by treatment with morphine chloridrate alone.

[Prevention of supraventricular tachysystole with anti-arrhythmia agents]. / Medikamentoznaia profilaktika supraventrikuliarnykh takhisistolii.

The paper substantiates the necessity of using a set of antiarrhythmic drugs for the prevention of supraventricular tachysystoles. In the development of supraventricular tachysystoles an important role is attributed to the disorders in automatic regulation of the sinus node. Cases are described in which the development of paroxysmal cardiac fibrillation with approximately equal intervals of time was caused by an inhibition of the sinus node activity. The set of antiarrhythmic drugs included beta-adrenergic blockers, isocholinic-type drugs, cardiac glycosides, Rauwolfia serpentina preparations, parasympatholitic drugs.

[Comparative evaluation of new drugs used in the treatment of cardiac arrhythmia].

The paper summarizes the experience gained in treating 830 patients with various cardiac rhythm disorders by employing new antirhythmic agents (propranolol, practolol, pindolol, alprenolol, oxyprenolol, benzoral, verapamil, lidocaine, imaline, sparteine, pulsonorma, disopyramide and quinidine durules). Comparative data on the efficacy of these agents are presented and indications and counterindications for their use are discussed.