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PubMed1988

Comparison of the analgesic efficacy of metamizole and tramadol in experimental pain.

The analgesic efficacy of 50 and 100 mg tramadol and 500 and 1,000 mg metamizole was compared using a randomized double-blind design on 10 volunteers; drugs were given orally as solutions. Constant painful stimuli were applied by controlled electrical stimulation of tooth pulp. Analgesia was monitored by verbal pain rating, by measurement of the current necessary to evoke sensation in a tooth and with the aid of the amplitude of somatosensory evoked potential. All 3 algesimetric methods showed in complete agreement higher analgesia by the 100-mg dose of tramadol compared to all other medications; 50 mg tramadol and 1,000 mg metamizole were equipotent analgesic doses. The mean relative potencies of metamizole and tramadol were found to be 1:23 in agreement with clinical studies. Pain relief was limited to 3-4 h for 100 mg tramadol; 500 and 1,000 mg metamizole and 50 mg tramadol had a shorter period of analgesia.

Administration, Oral↗
PubMed1995

Voglibose (AO-128) is an efficient alpha-glucosidase inhibitor and mobilizes the endogenous GLP-1 reserve.

The alpha-glucosidase inhibitor voglibose (AO-128) was designed to prevent rapid postprandial blood glucose rises in non-insulin-dependent diabetics. We analyzed its effect on the entero-insular axis in 72 healthy volunteers in a double-blind study design before, after the 1st dose, and on the 7th day of a 7-day treatment protocol (3 daily loads). Six parallel groups of 12 volunteers received voglibose (0.5, 1.0, 2.0, or 5.0 mg) or placebo (two groups). Blood was drawn at regular intervals up to 180 min after a standardized breakfast to analyze the levels of glucose, insulin, C peptide, gastric inhibitory polypeptide, and glucagon-like peptide 1 (GLP-1). As expected, after ingestion of voglibose, slight to moderate gastro-intestinal discomfort but no severe side-effects were reported. In a dose-dependent manner, voglibose significantly reduced postprandial increases of blood glucose, insulin, and C peptide. At the lower loads (0.5 and 1 mg voglibose three times daily), these effects were more pronounced after 7 days. The postprandial increase of gastric inhibitory polypeptide was already reduced after the first load of 2 and 5 mg voglibose. In comparison to the placebo group, this inhibition became also significant for the lower loads after 7 days. Interestingly, GLP-1, originating from the lower intestines, was increasingly released under voglibose treatment. The first administration of 1 mg voglibose enhanced GLP-1 secretion > 80% above controls. Treatment with 1 mg voglibose three times daily over 7 days revealed a maximal mobilizing effect on endogenous GLP-1 (> 90% above controls) which was not further increased by 2- or 5-mg loads. We conclude that voglibose treatment effectively inhibits intestinal disaccharidases and thereby mobilizes the endogenous pool of insulinotropic GLP-1.

Adolescent↗
PubMed2003

Drug-induced pneumonitis and heart failure simultaneously associated with venlafaxine.

Two cases of interstitial pneumonia with cardiac failure developing in patients treated with the new antidepressant venlafaxine are presented. A strong relationship between the development of the patients' illness and the initiation of venlafaxine treatment was identified. The cytochrome P (CYP) 450 system is involved in the metabolism of venlafaxine, suggesting that alterations in the drug metabolic clearance might be, at least in part, responsible for the development of drug-induced damage in these cases. This might occur either as a consequence of a genetic factor or concomitant drug therapy with an inhibitor of the related CYP system. After identifying the causative agent in the first case, withdrawal of the antidepressant together with corticosteroid treatment led to a favorable outcome. In the other case, the multiorgan failure became fatal. These cases highlight a hitherto undescribed association of an adverse lung reaction and heart failure due to venlafaxine.

Adult↗
PubMed1997

Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine.

OBJECTIVE: The rate of adverse events following discontinuation of treatment with extended-release venlafaxine was compared with the rate associated with discontinuation of placebo administration. METHOD: The subjects were 20 outpatients with major depressive disorder who had participated in a multicenter, double-blind, placebo-controlled study of the efficacy of the new extended-release formulation of venlafaxine. RESULTS: During the 3 days after discontinuation of treatment with the study drug, seven (78%) of the nine venlafaxine-treated subjects and two (22%) of the nine placebo-treated patients reported the emergence of adverse events, a statistically significant difference. CONCLUSIONS: These results suggest that clinicians discontinuing venlafaxine treatment should consider tapering the medication dose gradually.

Adult↗