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1.
Eur J Pharmacol ; 925: 175014, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35537490

RESUMO

The purpose of this study was to investigate the effects of oxymatrine and matrine on integrated cardiac function in rats using pressure-volume loop analysis. A pressure-volume loop catheter was advanced into the left ventricle in anesthetized rats. Steady-state hemodynamic and load-independent parameters were recorded before and after oxymatrine or matrine injection. Oxymatrine (200 mg/kg) and matrine (50, 100 mg/kg) significantly increased the preload recruitable stroke work, slope of maximal systolic pressure increase (dP/dtmax) - end-diastolic volume relationship, end-systolic elastance and volume axis intercept (V0), which are load-independent parameters. Furthermore, the observed increased cardiac efficiency, along with the decreased ventricular arterial coupling, pressure volume area and potential energy, reflect improved mechanoenergetics in oxymatrine (200 mg/kg) and matrine (25, 50 or 100 mg/kg) treated rats respectively. In addition, matrine (25, 50 mg/kg) decreased end-systolic volume and end-diastolic volume, and increased ejection fraction; matrine at 100 mg/kg further decreased end-systolic volume, end-diastolic volume, stroke volume and stroke work, shortened the time constant of left ventricular pressure decay, and increased dP/dtmax, and heart rate. These results suggest that both oxymatrine and matrine enhance left ventricular contractility and improve cardiac mechanical function. As the dose of matrine was much lower than that of oxymatrine, the effect of matrine on myocardial contractility was stronger than that of oxymatrine.


Assuntos
Alcaloides , Ventrículos do Coração , Contração Miocárdica , Quinolizinas , Função Ventricular Esquerda , Alcaloides/farmacologia , Animais , Ventrículos do Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Quinolizinas/farmacologia , Ratos , Volume Sistólico , Função Ventricular Esquerda/efeitos dos fármacos , Matrinas
2.
Eur J Pharmacol ; 895: 173869, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33454375

RESUMO

The purpose of this study was to investigate the analgesic interaction between matrine and paracetamol in an acetic acid-induced writhing model in mice. Fifty percent effective dose (ED50) values of the individual drugs were determined, and the different proportions of matrine and paracetamol were assayed using the isobolographic method. Our study demonstrated that both of matrine and paracetamol dose-dependently inhibited the writhing response evoked by acetic acid, and the ED50 values and their 95% confidence intervals against these tonic pain were 21.10 (17.86-24.92) mg/kg and 61.30 (50.71-74.10) mg/kg for matrine and paracetamol, respectively. At the fixed ratios of 1:1, 1:3 and 3:1, the experimental ED50 values of matrine and paracetamol combinations and their 95% confidence intervals were 10.52 (5.14-21.55) mg/kg, 9.13 (4.46-18.70) mg/kg and 4.98 (4.17-5.95) mg/kg, respectively, their theoretical ED50 values and 95% confidence intervals were 41.20 (36.31-46.74) mg/kg, 51.25 (44.19-59.44) mg/kg and 31.15 (27.25-35.60) mg/kg, and the experimental ED50 values of matrine and paracetamol combination were significantly lower than their calculated theoretical ED50 values (all P < 0.01), as revealed by isobolographic analysis. Furthermore, the experimental regression line was also significantly different from the calculated additive equal-effect line over the range of the tested doses (all P < 0.01). Our results suggest that the combination of matrine with paracetamol exerts analgesic synergistic interactions in a mouse acetic acid-induced writhing model, thereby offering a possible therapeutic alternative for the clinical management of inflammatory pain.


Assuntos
Acetaminofen/farmacologia , Alcaloides/farmacologia , Analgésicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Dor/prevenção & controle , Quinolizinas/farmacologia , Ácido Acético , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Masculino , Camundongos , Dor/induzido quimicamente , Dor/fisiopatologia , Dor/psicologia , Matrinas
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