Disease relevance of picotamide

• METHODS: Nine patients with essential hypertension who had cough after enalapril 20 mg once a day (coughers) were treated, while continuing the enalapril, in a double-blind crossover study with placebo or picotamide, 600 mg twice daily [1].
• Effect of picotamide on the clinical progression of peripheral vascular disease. A double-blind placebo-controlled study. The ADEP Group [2].
• We investigated the short-term effect of the TXB inhibitor picotamide on albuminuria induced by exercise in 15 microalbuminuric (i.e., with UAE at rest between 20 and 200 micrograms/min) type II diabetic patients (12 men and 3 women, age 56 +/- 2, BMI 28 +/- 1 kg/m2) and in six normal age-matched control subjects [3].
• At month 24, compared with randomized placebo, lesion numbers (P < .03) and percent stenosis (P < .01) in the picotamide group were significantly lower [4].
• The effect of picotamide on platelet function in patients with myeloproliferative disorders [5].

High impact information on picotamide

• The effects of picotamide occurred without significant side effects or changes in either blood pressure levels or glycometabolic control [6].
• Picotamide, a dual TXB synthetase inhibitor and TXB receptor antagonist, reduces exercise-induced albuminuria in microalbuminuric patients with NIDDM [3].
• The diabetic subjects performed five submaximal exercise tests (90% of theoretical heart rate) on a cycle ergometer: the first two under basal conditions; the third and fifth after subjects had received picotamide (900 mg/day) or placebo (3 tablets/day) for 10 days; the fourth exercise always was performed after 10 days of wash-out [3].
• In all patients, picotamide treatment was associated with an increase in diuresis and natriuresis (p < 0.001 vs. baseline) [7].
• Picotamide versus aspirin in diabetic patients with peripheral arterial disease: has David defeated Goliath [8]?

Chemical compound and disease context of picotamide

• CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease [9].
• We stress the unusual features of the reported case (HITT during prophylactic therapy with low doses of porcine heparin; intermittent thrombosis), and we suggest picotamide represents a rational therapy for HITT on the basis of clinical and pathogenetic considerations [10].
• In comparison to lamotrigine, the therapy with picotamide may have some advantages such as the use of the therapeutic dose from the first day of treatment (lamotrigine needs one month or more to reach such a dose) and the possibility to prevent cerebral ischaemic events and migraine stroke, a rare but severe complication of MwA attacks [11].

Biological context of picotamide

• Effects of picotamide (900 mg in 3 oral administrations for 7 days) on ex vivo and in vivo platelet TxA2 production and on platelet aggregation were evaluated in 8 patients with peripheral arteriopathy and in 8 normal subjects [12].
• Picotamide inhibits dose-dependently TxA2 synthesis by platelets (IC50: 1.5 x 10(-4) M) and enhances the formation of PGE2 [13].
• Binding kinetics and antiplatelet activities of picotamide, a thromboxane A2 receptor antagonist [14].
• We investigated the in vitro effect of picotamide on smooth muscle cell migration and proliferation [15].
• Picotamide (1-500 microM) decreased human and rat smooth muscle cell proliferation, evaluated as cell number, in a concentration-dependent and reversible manner [15].

Anatomical context of picotamide

• Picotamide did not inhibit potassium-induced contractions, thus excluding aspecific effects on vascular smooth muscle [16].
• Picotamide at 0.5 and 1.0 mM concentrations significantly (P less than 0.05) inhibited basal and LPS-stimulated synthesis of TxA2 measured by its stable immunoreactive (i) metabolite TxB2 in rat peritoneal macrophages [17].
• Picotamide, an antithromboxane agent, inhibits the migration and proliferation of arterial myocytes [15].
• No major bleeding occurred in patients on continuative therapy with picotamide, even in the presence of upper digestive tract disorders [18].
• Since our results clearly indicate that the action of picotamide persists even after washing out of the drug from the medium, the idea that this antagonistic effect may be dependent on its binding to platelet plasma membrane rather than on its cytosolic concentration, is strongly substantiated [19].

Associations of picotamide with other chemical compounds

• We have previously characterized the new antiplatelet agent picotamide as a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist in human platelets [20].
• All animals that responded to the combination of SQ29548 and dazoxiben, as well as those that responded to picotamide, received increasing intravenous infusions of epinephrine to restore CFVs.(ABSTRACT TRUNCATED AT 250 WORDS)[21]
• OKY046 alone or combined with BM13.505, picotamide and ridogrel, as well as PGD2, but not BM13.505 or aspirin, caused a stronger inhibition of platelet aggregation with desensitized platelets; this effect was potentiated by the phosphodiesterase inhibitor HL725 and was almost abolished by the adenylylcyclase inhibitor SQ22,536 [22].
• A Tx synthase inhibitor (OKY046), a PGH2/TxA2 receptor antagonist (BM13.505), their combination, two dual Tx synthase inhibitors/receptor antagonists (picotamide and ridogrel) or the cyclooxygenase inhibitor aspirin were studied [22].
• In PRP, the same picotamide concentration significantly enhanced ED50 for each aggregating agent (from 2.0 +/- 0.1 microM to 3.1 +/- 0.3 microM for ADP, p < 0.01; from 960 +/- 80 microM to 1,850 +/- 260 microM for Na arachidonate, p < 0.001; from 3.0 +/- 0.3 microgram/ml to 5.0 +/- 0.8 micrograms/ml for collagen, p < 0.01) [23].

Gene context of picotamide

• Polymorphism in anhydrous picotamide, i.e., nucleation of crystal forms A, mp 135.5 +/- 0.4 degrees C, and B, mp 152.9 +/- 0.3 degrees C after dehydration of PICOW, was detected by DSC and HSM [24].
• Picotamide decreased the response to each aggregating agent in both WB and PRP samples [23].
• Chronic administration of picotamide 1.2 g/d to patients with vascular disease resulted in a prompt and persistent fall in their increased plasma levels of beta-thromboglobulin [25].
• Effects of picotamide on release of endothelin-1, thromboxane and prostacycline after treadmill stress in patients with peripheral artery disease [26].

Analytical, diagnostic and therapeutic context of picotamide

• METHODS: By oral administration of picotamide (a renal TxA(2) synthase and TxA(2)/prostaglandin H(2) receptor inhibitor), we blocked renal TxA(2) [7].
• Determination of picotamide in human plasma and urine by high-performance liquid chromatography [27].
• In the present study the interaction between picotamide and TxA2 receptors on human platelets was investigated by a direct radioligand assay method with [125I]PTA-OH and [3H]U46619 as labelled radioligands [28].
• In the ADEP (Atherosclerotic Disease Evolution by Picotamide) trial, 2304 patients with peripheral obstructive arterial disease (POAD) were studied in a double-blind, placebo-controlled, 18-month, multicentre trial [29].
• Assessment of occlusion of the vascular access in patients on chronic hemodialysis: comparison of physical examination with continuous-wave Doppler ultrasound. STOP Investigators. Shunt Thrombotic Occlusion Prevention with Picotamide [30].

References