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The effect of the following drugs in therapeutic doses on somatosensory cortical evoked potentials was studied: methamphetamine, chlorpromazine, imipramine, diazepam, phenobarbital, pethidine, and novaminesulfone. Physiological saline was used as control. Each of these compounds was studied in 5 healthy subjects. Three evoked potentials were recorded before, and another three after administration of the drug. Each potential was averaged from 1024 single stimuli. None of the drugs, led to marked changes of the evoked potential, i.e., all data (latencies, amplitudes) were within the double standard deviation of the data obtained in normal subjects in a previous study. Although no significant changes were seen, some trends could be observed: methamphetamine and imipramine produced a decrease in the latency of the first positive peak, chlorpromazine increased the latency of the third positive peak. The amplitude of the third peak was reduced under phenobarbital. It is concluded that the drugs investigated in the presents study do not produce significant changes in the somatosensory cortical evoked potential and therefore drug application may be continued when evoked potentials are used for diagnostic purposes.

The profile of the spasmolytic 4,4-diphenyl-N-isopropyl-cyclohexylamine-hydrochloride (pramiverine, Sistalgin) is outlined on the basis of fundamental research. Evidence is provided that a combination with metamizole is useful in the case of Sistalgin comp. Description of the clinical and clinico-experimental examinations confirmed the margin of indications for Sistalgin and Sistalgin comp. Reference is made to the applications with a view to facilitate endoscopic and radiological procedures. The tabulated list of 2368 patients demonstrates the positive ratio between therapeutic effect and undesirable cholinolytic concomitant effect of Sistalgin comp.

The effect of the pyrazolone derivative metamizole on the motility of the upper gastrointestinal tract of the rat was investigated. An animal model for simultaneous quantification of gastric emptying and small intestinal transport was used. A test meal with different radioactive labels was administered by means of previously implanted tubes both to the stomach (1.0 ml; 51Cr) and to the duodenum (0.25 ml; 99mTc), and the spatial distribution of both isotopes in a gastrointestinal preparation was determined after a transport time of 30 min. It has been shown that intravenously administered metamizole reduces significantly the percentage of the test meal discharged by the stomach (control: 70.9 +/- 2.8; 50 mg/kg metamizole: 26.3 +/- 6.9, p less than 0.001; 250 mg/kg metamizole: 3.8 +/- 1.5, p less than 0.001); 1250 mg/kg metamizole: 1.1 +/- 0.3; p less than 0.001). The 50- and 250-mg/kg doses had no negative effect on the propulsion of the small intestine. A dose of 1250 mg/kg induced a significant reduction in small intestinal transport (p less than 0.001).

Salivary levels of the metabolites of metamizol (N-methyl-, N-acetyl- and 4-aminoantipyrine) were determined after the intake of film-coated metamizol (Novalgin) tablets and metamizol (Novalgin) solution. Cortical evoked potentials, pain ratings and thresholds of sensation were monitored following tooth pulp stimulation after administration of metamizol tablets. Within the different groups of subjects a remarkable degree of reproducibility was obtained for the metabolite concentrations in saliva. At 20 min after drug intake a more rapid absorption was demonstrable for the solution in comparison to the tablets. The metabolite levels were correlated to the simultaneously recorded pain response demonstrating that the analgesic efficacy can only be attributed to the two metabolites N-methyl- and -4-amino-antipyrine.

The following cardiovascular parameters were continuously measured in 12 dogs anaesthetized with sodium pentobarbital following i.v. application of Baralgin, a combination of 1-beta- piperidino-ethoxycarbmethoxy-benzophenone-hydrochloride with diphenylpiperidino-ethyl-acetamide-bromomethylate and 2.3-dimethyl-4-methylamino-1-phenyl-5-pyrazolone-N-methanesulfonic acid: Mean arterial blood pressure, left ventricular pressure, dp/dt-value in the left ventricle, the parameter (see article), told peripheral resistance, cardiac work, heart rate, cardiac output and stroke volume, flow rate in the A. femoralis and the repiration volume. In this experimental series dosages of 0.1, 0.25, 0.625 and 1.56 ml Baralgin/kg i.v. were tested and the subsequent cardiovascular activity was recorded for a period of 90 min following application. 1. The mean arterial blood pressure remained practically unaltered following low doses of Baralgin (0.1 and 0.25 ml/kg i.v.), whereas higher doses (0.625 and 1.56 ml/kg) led to an initial drop in blood pressure corresponding to the fall in total resistance. 2. The cardiac output rose slightly in correlation with rise in stroke volume. In the dosage range of 0.25 ml Baralgin/kg i.v. the rise in cardiac output was accentuated by an increase in heart rate. 3. The cardiac work remained relatively stable following small Baralgin doses, however, a slight diminution in cardiac work due to the fall in blood pressure and decrease in cardiac output, resulted from application of 1.56 mg/kg i.v. 4. A slight positive inotropic stimulation of the heart became apparent in the initial period following small doses of Baralgin (0.1 and 0.25 ml/kg i.v.), higher i.v. dosages caused a marginal reduction in cardiac contractility.

The study was designed to elicit any interference on the part of dipyrone with the antispasmodic activity of 2-(diethylamino)-1-methylethyl cis-1-hydroxy(bicyclohexyl)-2-carboxylate (rociverine) and on the part of rociverine with the analgesic activity of dipyrone. No evidence of any reciprocal inhibition of the specific pharmacodynamic activities of the two drugs emerged. Further, dipyrone exerted remarkable antispasmodic effect which in some experimental conditions supplements that of rociverine. The nature of this antispasmodic effect contributed by dipyrone could not be identified from the in vivo work, though in in vitro tests dipyrone revealed appreciable antihistaminic activity and weak muscle-relaxant activity. The value of an association in which neither activity is diminished and one is actually augmented is obvious.

In two pharmacological in vivo tests a comparative study was performed on the spasmolytic and analgesic effects of 4,4-diphenyl-N-isopropyl-cyclohexylamine-hydrochloride (pramiverine, Sistalgin), metamizole and a combination of both active principles in equal dose ratio (1 : 1000). The results demonstrated that pramiverine showed a potent spasmolytic effect which was potentiated by the combination with metamizole, and that the positive analgesic effect of metamizole was fully displayed in the combination with pramiverine, but that for pramiverine alone no analgesic effect was detected.

A device operated by compression has been studied in order to define a method of measuring analgesic effects. Three analgesics (metamizol, acetylsalicylic acid and ketobemidone) and placebo have been tested in man to verify the adequacy of this apparatus and its sensitivity.

The metabolites of dipyrone (metamizol, Novalgin) were compared with appropriate standard drugs for their influences on the pathways of the arachidonic acid metabolism. The drugs in this study had no significant effects on the lipoxygenase pathway in human neutrophils in vitro. The dipyrone metabolites 4-methylaminoantipyrine (MAAP) and 4-aminoantipyrine (AAP) inhibited prostaglandin synthesis in the 10(-3) to 10(-4) mol/l range thus being comparable to acetylsalicylic acid (ASA), whereas the two additional metabolites 4-acetylaminoantipyrine (AAAP) and 4-formylaminoantipyrine (FAAP) were practically inactive. This result is in accordance with the effects of the metabolites on the formation of oedema in the arthritis rat model, and supports published data showing that MAAP and AAP are the metabolites responsible for the clinical effects of dipyrone. Further systems in our study depending at least partially on the prostaglandin pathway were the release of antiaggregatory activity from rat aortae in vitro and the aggregation of human platelets induced by arachidonic acid in vitro. MAAP exhibits antiaggregatory activity (IC50 5 x 10(-6) mol/l), whereas the inhibitory effect on the vascular antiaggregatory release is much weaker. Compared to normals platelet aggregability ex vivo is enhanced in arthritic rats, but could significantly be lowered again by treatment of the rats with MAAP. A further system studied was the release of 6-keto-PGF1 alpha from rat mucosa in vitro and ex vivo. In vitro there is inhibition to be found with MAAP as well as with ASA. Ex vivo, however, dipyrone or MAAP slightly stimulates mucosal 6-keto-PGF1 alpha rather than inhibiting it, whereas ASA exerts inhibition, as expected.(ABSTRACT TRUNCATED AT 250 WORDS)