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The risk of agranulocytosis following the use of metamizole was studied by the method of controlled cases. All cases of agranulocytosis and their control cases in Sofia for the period 1982-1986 were included in the study. The mean agranulocytosis morbidity for this period was 3.16 cases for one million population for one year. The etiologic fraction was 7.1%. The relative risk of agranulocytosis following the use of metamizole is 1.25, the maximal risk is 0.03 cases for one million persons using metamizole for one year and the maximal lethal risk is 0.007 cases for one million persons using metamizole for one year. The use of metamizole in Bulgaria for the same period was studied, too. The data presented as a number of defined daily doses used by 1000 population for one day show that the use of metamizole in this country is high. A tendency toward an increase of 7.3% per year was found during the investigation. At the same time the agranulocytosis morbidity remained constant during the period of investigation. The results of the study lead to the conclusion that the use of metamizole is not related to a higher risk of agranulocytosis.

The effect of the combined preparation analgeton and its components--analgin (metamizol, noramidopyrindimethansulfonate) and aminton (2-amino-4-methyl-pyridinphosphate) was studied on the release of beta-endorphin and its influence on chronic hyperalgesia. Experiments were carried out in vivo and in vitro on white rats and it was established that analgin, aminton and analgeton stimulated the release of beta-endorphin, affecting various regulatory levels. Analgeton in contrast to analgin showed longer analgetic effect in animals with chronic hyperalgesia (adjuvant arthritis of white rats). Possibilities for pharmacological control of chronic pain by influencing the levels of endogenous opioids are discussed.

Analgin given repeatedly per os in dose 15 mg/kg to white male rats, causes changes in some indices of the liver NADPH-dependent mono-oxygenase system. At the end of the first month a decrease in the quantity of the microsomal protein was established as well as increase of the cytochrome's content P-450 and b5. The frequencies of cytochrome P-450-dependent biotransformations of substrates aminopyrine and aniline are also of different directions. At the end of the sixth month, because of multiple drug application all these indices are in the limits of the control values. A change in the catalytic features of cytochrome P-450, is established, which is expressed mainly by strongly decreased affinity to the substrates of first type. The Michaelis's constant Km for substrate aminopyrine depends on the duration of analgin introduction and increases up to 300% towards the control at the end of the sixth month.