Increase of adenosine plasma levels after oral trimetazidine: a pharmacological preconditioning?
| Autor: | Di Perri Tullio, Volpi Luciana, de Lalla Arianna, Blardi Patrizia, Auteri Alberto |
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| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Male
Adenosine Time Factors Vasodilator Agents Ischemia Trimetazidine Pharmacology Angina Pectoris medicine Humans Aged Analysis of Variance Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Mechanism of action Toxicity Ischemic preconditioning Liberation Female medicine.symptom business Nucleoside medicine.drug |
| Popis: | Trimetazidine (1-[2,3,4-trimethoxybenzyl] piperazine) (TMZ) is a cellular anti-ischemic agent able to prevent intracellular ATP decrease, limit intracellular acidosis, protect against oxygen-free radical-induced toxicity and inhibit neutrophil infiltration. However, its definitive mechanism of action had not been identified. Recent studies showed the existence of an endogenous mechanism of cellular protection against ischemia, defined as 'ischemic preconditioning'. This mechanism was related mainly to cellular liberation of adenosine, a nucleoside with protective effects in myocardial ischemia. Since TMZ acts by increasing cell tolerance to ischemia and adenosine is the mediator of ischemic preconditioning, in this study we investigated a possible interaction between TMZ and adenosine. Two groups of patients affected by angina pectoris, were admitted to the study. They received a single oral dose of TMZ. One group was treated, during different sessions, with TMZ 10 and 20 mg, the other group with TMZ 40 and 80 mg. After a 3 day wash-out from drug administration, each group received a placebo. Blood samples were collected at baseline (time 0) and 1, 2, 3, 4, 6, 8 h after drug administration, in order to detect plasma levels of adenosine by a high-performance liquid chromatography method. We observed that the administration of TMZ at doses of 10, 20, 40 and 80 mg induced an increase of adenosine plasma levels of 19, 50, 62 and 62%, respectively. We hypothesized that the activity of TMZ could depend, at least in part, on adenosine mediation and this interaction opens a new interpretation of the drug antischemic effect. |
| Databáze: | OpenAIRE |
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