Pharmaceutical compositions and methods of treating cardiovascular diseases
Provided herein is a pharmaceutical composition comprising two or more compounds, wherein each compound is independently a phosphodiesterase inhibitor, an adenosine receptor antagonist, a calcium channel blocker, a histamine H 1 -receptor agonist, a histamine H 2 -receptor agonist, a histamine H 3 -receptor antagonist, or a β 2 -adrenoreceptor agonist. Also provided herein is a method of treating, preventing, or ameliorating a cardiovascular disease in a subject, comprising administering to the subject in need thereof two or more compounds, wherein each compound is independently a phosphodiesterase inhibitor, an adenosine receptor antagonist, a calcium channel blocker, a histamine H 1 -receptor agonist, a histamine H 2 -receptor agonist, a histamine H 3 -receptor antagonist, or a β 2 -adrenoreceptor agonist.
1. A pharmaceutical composition for treating or ameliorating bradycardia or a cardiovascular disease, comprising:
a first compound comprising:
(i) theophylline or aminophylline 3.2-28.8 mg/dose, a subtherapeutically effective amount;
(ii) nifedipine 0.16-2.88 mg/dose, a subtherapeutically effective amount;
(iii) betahistine 0.4-10.8 mg/dose, a subtherapeutically effective amount;
(iv) levalbuterol or albuterol 0.03-1.08 mg/dose, a subtherapeutically effective amount.
2. A pharmaceutical composition for treating or ameliorating bradycardia or a cardiovascular disease, comprising:
(i) theophylline or aminophylline 28.8-80 mg/dose, a subtherapeutically effective amount;
(ii) nifedipine 1.44-12 mg/dose, a subtherapeutically effective amount;
(iii) betahistine 3.6-40 mg/dose, a subtherapeutically effective amount;
(iv) levalbuterol or albuterol 0.27-3.8 mg/dose, a subtherapeutically effective amount.
3. A pharmaceutical composition for treating or ameliorating bradycardia or a cardiovascular disease, comprising:
(i) theophylline or aminophylline 80-192 mg/dose, a subtherapeutically effective amount;
(ii) nifedipine 4-38.4 mg/dose, a subtherapeutically effective amount;
(iii) betahistine 10-120 mg/dose, a subtherapeutically effective amount;
(iv) levalbuterol or albuterol 0.75-9 mg/dose, a subtherapeutically effective amount.
4. The pharmaceutical composition for treating or ameliorating bradycardia or a cardiovascular disease of claim 1 , further comprising as a kit:
a medium-dose compound comprising:
(i) theophylline or aminophylline 28.8-80 mg/dose, a subtherapeutically effective amount;
(ii) nifedipine 1.44-12 mg/dose, a subtherapeutically effective amount;
(iii) betahistine 3.6-40 mg/dose, a subtherapeutically effective amount;
(iv) levalbuterol or albuterol 0.27-3.8 mg/dose, a subtherapeutically effective amount.
5. The pharmaceutical composition for treating or ameliorating bradycardia or a cardiovascular disease of claim 1 , further comprising as a kit:
a high-dose compound comprising:
(i) theophylline or aminophylline 80-192 mg/dose, a subtherapeutically effective amount;
(ii) nifedipine 4-38.4 mg/dose, a subtherapeutically effective amount;
(iii) betahistine 10-120 mg/dose, a subtherapeutically effective amount;
(iv) levalbuterol or albuterol 0.75-9 mg/dose, a subtherapeutically effective amount.
6. The pharmaceutical composition for treating or ameliorating bradycardia or a cardiovascular disease of claim 4 , further comprising as a kit:
a high-dose compound comprising:
(i) theophylline or aminophylline 80-192 mg/dose, a subtherapeutically effective amount;
(ii) nifedipine 4-38.4 mg/dose, a subtherapeutically effective amount;
(iii) betahistine 10-120 mg/dose, a subtherapeutically effective amount;
(iv) levalbuterol or albuterol 0.75-9 mg/dose, a subtherapeutically effective amount.