[Pharmacology of selegiline (recent considerations)]. / A selegilin farmakológiája (újabb szempontok).

The nigrostriatal system, where dopaminergic neuron activity dominates, plays and important role in control of motoric and psychic functions. Selegiline with its neurochemical activity ie. MAO-B enzyme and dopamine uptake inhibition is able to restore or improve the deteriorated function of that system. Selegiline can hinder the uptake of tyramine into the peripheral sympathetic nerve endings, so cheese effect, which is a characteristic and dangerous side effect induced by MAO-A inhibitors, does not occur. Selegiline can potentiate the learning activity of PEA in rats, these effect may be connected with increased dopamine turnover in the striatum. In pathological conditions dopamine can be replaced by L-dopa, so it has a fundamental role in the improvement of dopaminergic functions. According to neurochemical activity selegiline takes a prominent role in the extension and improvement of L-dopa therapy. The neuroprotective effect of selegiline is multiple, with the inhibition of MAO-B it can stop the production of neurotoxin MPP+ (arising from MPTP) and its uptake into the nerve endings respectively. In chronic treatment with Selegiline SOD activity increases in rats, as a consequence the level of free oxygen radicals and toxic metabolites can be diminished. Chronic treatment with selegiline does not influence the activity of young animals, but improves sexual activity and learning capacity and enlarges life expectancy of old rats. These experiments verified its positive activity on the nigrostriatal system and give a good chance for geriatric usage. In longtime treatments dependency was not stated.

Comparative studies of drotaverine--acephyllinate (Depogen) and pentoxifylline (Trental).

Pentoxifylline is an orally active agent for the treatment of peripherial and cerebral vascular diseases. Pentoxifylline increases the deformability of red blood cells in vitro, reduces blood viscosity and decreases platelet aggregation and thrombus formation. Depogen has shown antiaggregatory effect both in vitro and in ex vivo. The inhibitory effect of Pentoxifylline was about 3-5 times weaker than that of Depogen. IC50 = 900/micrograms/ml for Depogén and 3600/micrograms/ml for Pentoxifylline on human platelet rich plasma. Depogen has shown ex vivo antiaggregatory effect on anesthetised rabbits, ID50 = 7 mg/kg in case of iv. administration, and ID50 = 300 mg/kg in case of orally administration. Both compound inhibit the release of platelet precoagulation factor, but the effect of Pentoxifylline was slighter.

Cardioprotective effect of prostacyclin and 7-oxo-PGI2 in rats against chronic isoproterenol damage.

Isoproterenol (ISO) was injected in 5 mg/kg i.p. doses to rats, daily for two weeks. We evaluated the developed myocardial hypoxia and necrosis quantitatively by histological methods. To follow the time course of cardioprotection prostacyclin or 7-oxo-PGI2 were injected daily, i.p. 5, 30 min and 1, 2, 3, 4 hours before or after the ISO to groups of ten rats, respectively. Cardioprotection was defined as the reduction of necrotized areas and was expressed as percentage change compared to the control (saline treated) group. 1 microgram/kg PGI2 and 50 micrograms/kg 7-oxo-PGI2+ showed nearly equipotent cardioprotection (37.3-7.9% and 38.3-6.8%, respectively). The peak effect of both compounds appeared when injected prior to ISO in the 120. min but the action of 7-oxo-PGI2 was more prolonged. The different doses of prostacyclin analogs given after the ISO injection were ineffective with the exception of 50 micrograms/kg 7-oxo-PGI2 (29.75 +/- 5.2%).

The role of central dopamine (DA) receptors in the regulation of blood pressure.

GYKI-32 887 reveals an antihypertensive action, similar to that of the known ergoline derivatives, in conscious SH-rats, in anesthetized normotensive rats, and in cats. It exerts its action first of all by stimulation of the central DA-receptors and by this it reduces the sympathetic activity. The hypotensive effect cannot be detected after icv administration, but both the hypotension and bradycardia can be antagonized by sulpiride administered either icv or iv.

Cardiovascular effects of a potent opioid peptide, (D-Met2, Pro5)-enkephalinamide.

The cardiovascular effects of morphine and a potent enkephalin analogue, D-Met2, Pro5-enkephalinamide (D-Met2, Pro5-EA) have been examined in pentobarbitone anesthetized cats with their vagi cut and in awake normotensive and genetically hypertensive rats. In cats both opioids only moderately decreased the blood pressure and the heart rate, but the enkephalin analogue considerably attenuated the carotid occlusion pressor response. Neither substance influenced the blood pressure and the heart rate in normotensive rats, but both induced moderate hypotension and considerable bradycardia in spontaneously hypertensive rats, the potency of D-Met2, Pro5-EA being much stronger than that of morphine. These observations confirm the conclusions from the literature that, under physiological conditions, endorphins play no primary role in the regulation of the cardiovascular functions but they might be mobilized in certain cases of pathological elevation of the blood pressure probably as a part of a compensatory process.