Table 3.

Drugs affecting OXPHOS, MMP and mPTP, their clinical manifestations, and relevant in vitro and in vivo studies.

Modules	Alterations	Pharmacology	Drugs	Clinical Manifestations	Cmax	Models	Dose	Time	References
OXPHOS	Inhibition of complex I	Cholesterol medications	Simvastatin	Cardiac atrophy	0.02 μM	H9c2	10 μM	24 h	[151]
OXPHOS	Inhibition of complex I	β-adrenoceptor agonists	Isoproterenol	HF	0.01 μM	Male Wistar rats (SC)	100 mg/kg, BID	12 h	[83]
OXPHOS	Inhibition of complex I	Alkylating agent	Cyclophosphamide	HMC, CMP	143 μM	Male Wistar rats (IP)	200 mg/kg	10 d	[111]
						Male Wistar rats (IP)	200 mg/kg	10 d	[124]
OXPHOS	Inhibition of complex I	NRTIs	Zidovudine	CMP	4 μM	Isolated mitochondria from H9c2	50 μM	3 passages	[152]
			Didanosine	CMP	12 μM	Isolated mitochondria from H9c2	50 μM	3 passages	[152]
OXPHOS	Inhibition of complex I	Anthracyclines	DOX	CHF, decreased LVEF, ST, myocarditis, CMP	15.3 μM	Male Wistar rats (IP)	2.5 mg/kg/2 d	2 w	[95]
OXPHOS	Inhibition of complex I	Chemotherapeutic agents	As2O3	QT prolongation TdP, CMP, tachycardia	12.1 μM	Isolated mitochondria from H9c2	5 μM	24 h	[141]
OXPHOS	Inhibition of complex I	Anesthesia	Propofol	HF, arrhythmia	30.13 μM	Cardiac muscle fibers of Wistar male rats	0.025 mM		[153]
			Halothane (fluothane)	-	10 μM	Pig heart submitochondrial particles	Dose response curve		[154]
	Inhibition of complex I	TKIs	Mubritinib	-	-	H9c2	0.5 μM		[140]
OXPHOS	Inhibition of complex I	NSAIDs	Nabumetone	-	2.45 μM	Submitochondrial particles	55 nmol/mg protein inhibit 50%		[142]
			Meclofenamate sodium	-	3.55 μM	Mitochontria	100 µM (70% inhibition)		[138]
			Naproxen	-	100 µM	Mitochontria	200 µM (50% inhibition)		[138]
OXPHOS	Inhibition of complex I	Addictive drugs	Cocaine	Arrhythmias, angina, MI, HF	0.76–0.94 µM	Isolated rat heart mitochondria	1 μM		[155]
OXPHOS	Inhibition of complex I	Anti-arrhythmic drug	Amiodarone	LQT, TdP, Hypotension, AV block, Arrhythmia, heart block, SBC, CHF, VF	4.65 μM	Isolated rat heart mitochondria	IC50 = 5.24 µM		[139]
			Dronedarone	AF, HF	0.15–0.26 μM	Isolated rat heart mitochondria	IC50 = 3.07 µM		[139]
OXPHOS	Inhibition of complex I	Immunosuppressant drug	Cyclosporine A	Cardiotoxicity	0.5–5 µM	Enzymes and coenzymes	100 µM		[156]
OXPHOS	Inhibition of complex II	NSAIDs	Diclofenac	Hypertension, arrhythmias	7.9 µM	Isolated rat heart mitochondria	10 µg/mL	1 h	[115]
			Naproxen	-	100 µM	Isolated rat heart mitochondria	50 μM	1 h	[60]
OXPHOS	Inhibition of complex II	Alkylating agent	Cyclophosphamide	HMC, CMP Cardiotoxicity	143 μM 0.22 μM	Male Wistar rats (IP)	200 mg/kg	10 d	[124]
						Male Wistar rats (IP)	200 mg/kg	10 d	[111]
OXPHOS	Inhibition of complex II	β receptor blocker drugs	Propranolol			Isolated rat heart mitochondria	10 µg/mL	30 min	[119]
			Atenolol	Cardiotoxicity	4.99 μM	Isolated rat heart mitochondria	10 µg/mL	30 min	[119]
OXPHOS	Inhibition of complex II	Macrolide antibiotics	Azithromycin	Arrhythmia	0.32–0.87 μM	Isolated rat heart mitochondria	25 μM	20 min	[120]
			Clarithromycin	TdP	2.67–13.37 μM	Isolated rat heart mitochondria	50 μM	20 min	[120]
			Erythromycin	TdP	11 μM	Isolated rat heart mitochondria	25 μM	20 min	[120]
OXPHOS	Inhibition of complex III	Chemotherapeutic agents	As2O3	QT prolongation TdP, CMP, tachycardia	12.1 μM	Isolated mitochondria from H9c2	5 μM	24 h	[141]
OXPHOS	Inhibition of complex III	TKIs	Sorafenib	Bleeding, hypertension, QT prolongation, CHF, CI, MI	16.6 μM	NRVMs	4.5 µM	20 min	[32]
OXPHOS	Inhibition of complex III	Alkylating agent	Cyclophosphamide	HMC, CMP	143 μM	Male Wistar rats (IP)	200 mg/kg	10 d	[111]
					7.9 µM	Male Wistar rats (IP)	200 mg/kg	10 d	[124]
OXPHOS	Inhibition of complex III	NSAIDs	Diclofenac	Hypertension, arrhythmias		Mitochondria isolated from mouse hearts	5 µM		[157]
			Meclofenamate sodium	-	3.55 μM	Mitochontria	10 µM		[138]
	Inhibition of complex III	Anthracyclines	DOX	CHF, decreased LVEF, ST, myocarditis, CMP	15.3 μM	-	15 mg/kg	-	[158]
OXPHOS	Inhibition of complex IV	Alkylating agent	Cyclophosphamide	HMC, CMP HF	143 μM 0.01 μM	Male Wistar rats (IP)	200 mg/kg	10 d	[111]
						Male Wistar rats (IP)	200 mg/kg	10 d	[124]
OXPHOS	Inhibition of complex IV	β-adrenoceptor agonists	Isoproterenol			Male Wistar rats (SC)	100 mg/kg, BID	12 h	[83]
OXPHOS	Inhibition of complex IV	Cholesterol medications	Simvastatin	Cardiac atrophy	0.02 μM	H9c2	10 μM	24 h	[151]
OXPHOS	Inhibition of complex IV	Anthracyclines	DOX	CHF, decreased LVEF, ST, myocarditis, CMP, QT prolongation TdP, CMP, tachycardia	15.3 μM 12.1 μM	Male Wistar rats (IP)	2.5 mg/kg/2 d	2 w	[95]
						Male Wistar rats (IV)	1 mg/kg/w	7 w(started at 11 w, observed at 48 w)	[96]
OXPHOS	Inhibition of complex IV	Chemotherapeutic agents	As2O3			Isolated mitochondria from H9c2	5 μM	24 h	[141]
OXPHOS	Inhibition of complex IV	NSAIDs	Celecoxib	Thrombosis, MI, stroke	3–5 µM	Isolated rat heart mitochondria	16 µg/mL		[14]
OXPHOS	Inhibition of complex IV	Proteasome inhibitor	Bortezomib	QT prolongation, hypotension	0.3 μM	Male Wistar rats	0.2 mg/kg	3 w	[159]
OXPHOS	Inhibition of complex IV	Immunosuppressant drug	Cyclosporine A	Cardiotoxicity	0.5–5 µM	Enzymes and coenzymes	100 µM		[156]
OXPHOS	Inhibition of complex V	Chemotherapeutic agents	Mitoxantrone	CHF, CMP, decreased LVEF, arrhythmia	3.3 μM	Isolated rat heart mitochondria	2.5 mg/kg on d 0, 10, and 20	22 d	[160]
OXPHOS	Inhibition of complex V	Anticonvulsants	Phenytoin	Bradycardia, hypotension	87.21 μM	guinea pig heart preparations	1.0 nM		[161]
OXPHOS	Downregulation of complex I expression	TKIs	Regorafenib	MI; hypertension	8.08 μM	H9c2	20 μM	72 h	[90]
OXPHOS	Downregulation of complex I expression	Nucleoside analogues	Remdesivir	Bradycardia, QT prologation, CA	9 μM	HiPSC-CMs	2.5 μM	3 d	[86]
OXPHOS	Downregulation of complex I expression	Addictive drugs	Ethanol			Male C57BL/6J mice	10% (v/v)	12 w	[162]
OXPHOS	Downregulation of complex I expression	Anthracyclines	DOX	CHF, decreased LVEF, ST, myocarditis, CMP	15.3 μM	Male CD-1 mice (IP)	9 mg/kg	1 w	[100]
			Mitoxantrone	CHF, CMP, decreased LVEF, arrhythmia	3.3 μM	Male CD-1 mice (IP)	6 mg/kg	1 w	[100]
OXPHOS	Downregulation of complexe II expression	Anesthesia	Propofol	HF, arrhythmia	30.13 μM	HiPSC-CMs	10 µg/mL	48 h	[163]
		Addictive drugs	Ethanol			Male C57BL/6J mice	10% (v/v)	12 w	[162]
OXPHOS	Downregulation of complex III expression	Addictive drugs	Ethanol			Male C57BL/6J mice	10% (v/v)	12 w	[162]
		Anthracyclines	DOX	CHF, decreased LVEF, ST, myocarditis, CMP	15.3 μM	Male CD-1 mice (IP)	9 mg/kg	1 w	[100]
OXPHOS	Downregulation of complex IV expression		Mitoxantrone	CHF, CMP, decreased LVEF, arrhythmia	3.3 μM	Male CD-1 mice (IP)	6 mg/kg	1 w	[100]
		Anthracyclines	DOX	CHF, decreased LVEF, ST, myocarditis, CMP	15.3 μM	Male Wistar rats (IV)	1 mg/kg/w	7 w(started at 11 w, observed at 48 w)	[96]
		Addictive drugs	Ethanol			Male C57BL/6J mice	10% (v/v)	12 w	[162]
OXPHOS	Downregulation of complex V expression	Nucleoside analogues	Remdesivir	Bradycardia, QT prologation, CA	9 μM	HiPSC-CMs	2.5 μM	3 d	[86]
OXPHOS	Downregulation of complex V expression	TKIs	Regorafenib	MI; hypertension	8.08 μM	H9c2	20 μM	72 h	[90]
OXPHOS	Downregulation of complex V expression	Proteasome inhibitor	Bortezomib	QT prolongation, hypotension	0.3 μM	Male Wistar rats	0.2 mg/kg	1 w	[159]
OXPHOS	Downregulation of complex V expression	Anthracyclines	DOX	CHF, decreased LVEF, ST, myocarditis, CMP	15.3 μM	Male CD-1 mice (IP)	9 mg/kg	1 w	[100]
			Mitoxantrone	CHF, CMP, decreased LVEF, arrhythmia	3.3 μM	Male CD-1 mice (IP)	6 mg/kg	1 w	[100]
OXPHOS	Downregulation of complex V expression	Nucleoside analogues	Remdesivir	Bradycardia, QT prologation, CA	9 μM	HiPSC-CMs	2.5 μM	3 d	[86]
OXPHOS	Downregulation of complex V expression	Addictive drugs	Ethanol			Male C57BL/6J mice	10% (v/v)	12 w	[162]
OXPHOS	Inhibition of OXPHOS	Anti-arrhythmic drug	Clofilium	TDP	1 μM	-	-	-	[64]
OXPHOS	Inhibition of OXPHOS	Antipsychotics	Aripiprazole	-	2.24 μM	-	-	-	[64]
OXPHOS	Inhibition of OXPHOS	TKIs	Sorafenib	Bleeding, hypertension, QT prolongation, CHF, CI, MI	16.6 μM	HiPSC-CMs	10 µM	24 h	[164]
OXPHOS	OCR reduction	NSAIDs	Acetylsalicylate	-	0.5–10 mM	Isolated rat heart mitochondria	5 mM		[165]
OXPHOS	OCR reduction	NRTIs	Zidovudine	CMP	4 μM	H9c2	50 μM	3 passages	[152]
						TMPK-overexpressing H9c2 cells	100 µM	24 h	[131]
			Didanosine	CMP	12 μM	H9c2	50 μM	3 passages	[152]
OXPHOS	OCR reduction	Nucleoside analogues	Remdesivir	Bradycardia, QT prologation, CA	9 μM	HiPSC-CMs	2.5 μM	3 d	[86]
OXPHOS	OCR reduction	Cholesterol medications	Simvastatin	Cardiac atrophy	0.02 μM	H9c2	10 μM	24 h	[151]
OXPHOS	OCR reduction	Analgesics	Salicylic acid	-	0.5–10 mM	Isolated rat heart mitochondria	5 mM		[165]
OXPHOS	OCR reduction	Local anesthetics	Bupivacaine (marcaine)	VF	0.7 μM	neonatal mouse cardiomyocytes	5 μM		[166]
OXPHOS	Reduction in ATP content	Anesthesia	Propofol	HF, arrhythmia	30.13 μM	Isolated rat heart mitochondria	300 μM		[167]
OXPHOS	Reduction in ATP content	Local anesthetics	Lidocaine	VF	36 μM	-	-	-	[168]
OXPHOS	Reduction in ATP content	Anthracyclines	DOX	CHF, decreased LVEF, ST, myocarditis, CMP	15.3 μM	-	15 mg/kg	-	[158]
OXPHOS	Reduction in ATP content	Chemotherapeutic agents	Etoposide	Hypotension	17 μM	hiPSC-CMs	30 μM	48 h	[169]
OXPHOS			Mitoxantrone	CHF, CMP, decreased LVEF, arrhythmia	3.3 μM				[160]
OXPHOS	Reduction in ATP content	Alkylating agent	Cyclophosphamide	HMC, CMP CMP, LVD, CHF	143 μM	Male Wistar rats (IP)	200 mg/kg	1 w	[170]
						Male Wistar rats (IP)	200 mg/kg	1 w	[171]
OXPHOS	Reduction in ATP content	Monoclonal antibody	Trastuzumab		2.59 mM	-	-	-	[172]
OXPHOS	Reduction in ATP content	TKIs	Imatinib mesylate	QT prolongation, CHF, decreased LVEF	2.71 μM	NRVMs	5 μM	24 h	[91]
			Sunitinib	Decreased LVEF, QT prolongation, TdP, hypertension, HF, CMP Bleeding, hypertension, QT prolongation, CHF, CI, MI	0.25 μM	Male SD rats (oral)	10 mg/kg/d	3 w	[89]
						Male Wistar Rats (oral)	25 mg/kg/d	28 d	[173]
						NRVMs	60% of ATP was depleted at 23 µM	24 h	[174]
			Sorafenib		16.6 μM	Male SD rats (oral)	10 mg/kg/d	3 w	[89]
			Regorafenib	MI; hypertension	8.08 μM	H9c2	5 μM	48 h	[90]
OXPHOS	Reduction in ATP content	NSAIDs	Naproxen	-	100 µM	Isolated rat heart mitochondria	50 μM	1 h	[60]
			Celecoxib	Thrombosis, MI, stroke	3–5 µM	Isolated rat heart mitochondria	25 μM	1 h	[60]
			Diclofenac	Hypertension, arrhythmias -	7.9 µM	Isolated rat heart mitochondria	100 μM	1 h	[60]
						-	-	-	[142]
						-	-	-	[175]
			Piroxicam		5 µM	-	-	-	[142]
			Indomethacin	Hypertension	6 µM	-	-	-	[142]
			Nimesulide	-	21.08 µM	-	-	-	[142]
			Meloxicam	HA, stroke	6.55 µM	-	-	-	[142]
OXPHOS	Reduction in ATP content	NRTIs	Zidovudine	CMP Bradycardia, QT prologation, CA	4 μM	Rats (oral)	125 mg/kg/d	4 w	[116]
						TMPK-overexpressing H9c2 cells	Dose response curve(IC50 = 70 μM)	4 d	[131]
OXPHOS	Reduction in ATP content	Nucleoside analogues	Remdesivir		9 μM				[176]
OXPHOS	Reduction in ATP content	Addictive drugs	Ethanol	Arrhythmias, angina, MI, HF		Male C57BL/6J mice	10% (v/v) for first w, 14% (v/v) for second w, 18% (v/v) for third w,	12 w	[162]
						H9c2	184.34 mM	24 h	[177]
			Cocaine	LQT, TdP, Hypotension, AV block, Arrhythmia, heart block, SBC, CHF, VF	0.76–0.94 µM	H9c2	1.79 mM	24 h	[177]
						Isolated rat heart mitochondria	2*7.5 mg/kg/d	7 d	[178]
						Isolated rat heart mitochondria	2*7.5 mg/kg/d	7 d	[179]
OXPHOS	Reduction in ATP content	Anti-arrhythmic drug	Amiodarone		4.65 μM	H9c2	IC50 = 1.84 µM	4 h	[139]
			Dronedarone	AF, HF	0.15–0.26 μM	H9c2	IC50 = 0.49 µM	4 h	[139]
OXPHOS	Reduction in ATP content	β-adrenoceptor agonists	Isoproterenol	HF	0.01 μM	Male Wistar rats (SC)	100 mg/kg, BID	12 h	[82]
OXPHOS	Reduction in ATP content	Cholesterol medications	Simvastatin	Cardiac atrophy	0.02 μM	H9c2	10 μM (6 h); 100 μM (24 h)		[151]
OXPHOS	Uncoupling of OXPHOS	TKIs	Crizotinib	QT prolongation	0.73 μM	-	-	-	[64]
OXPHOS	Uncoupling of OXPHOS	NSAIDs	Acetylsalicylate	-	0.5–10 mM	Isolated rat heart mitochondria	10 mM		[165]
			Diclofenac	Hypertension, arrhythmias	7.9 µM	-	-	-	[142]
			Piroxicam	-	5 µM	-	-	-	[142]
			Indomethacin	Hypertension	6 µM	-	-	-	[142]
			Nimesulide	-	21.08 µM	-	-	-	[142]
			Meloxicam	HA, stroke	6.55 µM	-	-	-	[142]
			tenidap	-	8.44 µM (30525499)	-	-	-	[64]
OXPHOS	Uncoupling of OXPHOS	NRTIs	Zidovudine	CMP	4 μM	H9c2	50 lM	18 h	[180]
			Didanosine	CMP	12 μM		50 lM	18 h	[180]
OXPHOS	Uncoupling of OXPHOS	Addictive drugs	Ethanol			Isolated mitochondria from rabbit ventricle	10 µM	2 h	[181]
OXPHOS	Uncoupling of OXPHOS	Anti-arrhythmic drug	Amiodarone	LQT, TdP, Hypotension, AV block, Arrhythmia, heart block, SBC, CHF, VF	4.65 μM	Isolated rat heart mitochondria	1 µM		[139]
			Dronedarone	AF, HF	0.15–0.26 μM	Isolated rat heart mitochondria	0.1 µM		[139]
OXPHOS	Uncoupling of OXPHOS	Analgesics	Salicylic acid	-	0.5–10 mM	Isolated rat heart mitochondria	10 mM		[165]
MMP	Dissipation of MMP	Anthracyclines	DOX	CMP, MI, CHF, VA, pericarditis, myocarditis	15.3 μM	Kunming mice (IP)	2 mg/kg	10 d	[102]
						KIND-2-derived cardiac cells	0.24 μM disrupte 48.3%	48 h	[182]
			Daunorubicin		89 μM	Neonatal rat cardiac cells	4 μM	24 h	[97]
MMP	Dissipation of MMP	Chemotherapeutic agents	Cisplatin	Decreased LVEF, arrhythmias, ECA, myocarditis, CMP Hypotension	27.54 μM	C57BL mice (IV)	10 mg/kg/d	1 W	[112]
						NRVMs	200 μM	24 h	[183]
			Etoposide		17 μM	HiPSC-CMs	10 μM	48 h	[169]
			As2O3	QT prolongation TdP, CMP, tachycardia	12.1 μM	H9c2	5 μM	24 h	[184]
MMP	Dissipation of MMP	Monoclonal antibody	Trastuzumab	CMP, LVD, CHF	2.59 mM	H9c2	200 nM	24 h	[185]
MMP	Dissipation of MMP	TKIs	Imatinib mesylate	QT prolongation, CHF, decreased LVEF	2.71 μM	NRVMs	5 μM	18 h	[91]
			Sunitinib	Decreased LVEF, QT prolongation, TdP, hypertension, HF, CMP	0.25 μM	Male SD rats (oral)	10 mg/kg/d	3 W	[89]
			Regorafenib	MI; hypertension	8.08 μM	H9c2	20 μM	72 h	[90]
MMP	Dissipation of MMP	NSAIDs	Diclofenac	Hypertension, arrhythmias -	7.9 µM		-	-	[142]
							Isolated rat heart mitochondria	10 µg/mL	[115]
							Mitochondria isolated from mouse hearts	10 µg/mL	[157]
							C57BL/6 mice (oral)	15 mg/kg/D	[175]
							Immortalized human cardiomyocytes	100 μM	[85]
			Piroxicam		5 µM		-	-	[142]
			Indomethacin	Hypertension	6 µM		-	-	[142]
			Nimesulide	-	21.08 µM		-	-	[142]
			Meloxicam	HA, stroke	6.55 µM		-	-	[142]
			Meclofenamate sodium	-	3.55 μM		H9c2	5 µM (40% inhibition)	[138]
			Naproxen	-	100 µM	Isolated rat heart mitochondria	25 μM (60 min); 100 μM (30 min)		[60]
			Diclofenac			Isolated rat heart mitochondria	50 μM	5 min	[60]
			Celecoxib	Thrombosis, MI, stroke	3–5 µM	Isolated rat heart mitochondria	25 μM	5 min	[60]
MMP	Dissipation of MMP	NRTIs	Zidovudine	CMP	4 μM	TMPK-overexpressing H9c2 cells	100 µM	24 h	[131]
MMP	Dissipation of MMP	Anti-arrhythmic drug	Amiodarone	LQT, TdP, Hypotension, AV block, Arrhythmia, heart block, SBC, CHF, VF	4.65 μM	H9c2	IC50 = 2.94 μM	6 h	[139]
			Dronedarone	AF, HF	0.15–0.26 μM	H9c2	IC50 = 0.5 μM	6 h	[139]
MMP	Dissipation of MMP	β receptor blocker drugs	Propranolol	Cardiotoxicity	0.22 μM	Isolated rat heart mitochondria	5 µg/mL	5 min	[119]
			Atenolol	Cardiotoxicity	4.99 μM	Isolated rat heart mitochondria	5 µg/mL	5 min	[119]
MMP	Dissipation of MMP	Aconitum species	Aconitum sp.	VA	19.27 μg/ml	H9c2	10 μM	24 h	[186]
MMP	Dissipation of MMP	Cholesterol medications	Simvastatin	Cardiac atrophy	0.02 μM	H9c2	10 μM	24 h	[151]
MMP	Dissipation of MMP	Diabetes medication	Pioglitazone	HF	2.6 μM	Isolated rat heart mitochondria	12.5 µg/mL	5 min	[122]
MMP	Dissipation of MMP	Anesthesia	Propofol	HF, arrhythmia	30.13 μM	Isolated rat heart mitochondria	300 μM		[167]
MMP	Dissipation of MMP	β-adrenoceptor agonists	Isoproterenol	HF	0.01 μM	Isolated rat heart mitochondria	85 mg/kg/d	2 d	[187]
mPTP	Increases in mPTP opening	NRTIs	Zidovudine	CMP	4 μM	TMPK-overexpressing H9c2 cells	100 µM	24 h	[131]
mPTP	Increases in mPTP opening	Chemotherapeutic agents	As2O3	QT prolongation TdP, CMP, tachycardia	12.1 μM	Male BALB/c mice	2 mg/kg (14 d); 4 mg/kg (3 d)		[84]
mPTP	Increases in mPTP opening	Monoclonal antibody	Trastuzumab	CMP, LVD, CHF	2.59 mM	-	-	-	[22]
mPTP	Loss of cytochrome c	Anthracyclines	DOX	CHF, decreased LVEF, ST, myocarditis, CMP	15.3 μM	Isolated rat heart mitochondria, subcutaneously (SC)	2 mg/kg/w	7 w	[188]
mPTP	Loss of cytochrome c	Chemotherapeutic agents	Cisplatin	Decreased LVEF, arrhythmias, ECA, myocarditis, CMP	27.54 μM	NRVMs	200 μM	24 h	[183]
mPTP	Loss of cytochrome c	TKIs	Imatinib mesylate	QT prolongation, CHF, decreased LVEF	2.71 μM	NRVMs	5 μM	24 h	[91]
mPTP	Loss of cytochrome c	NRTIs	Zidovudine	CMP	4 μM	Rats (oral)	125 mg/kg/d		[116]
mPTP	Loss of cytochrome c	β receptor blocker drugs	Propranolol	Cardiotoxicity	0.22 μM	Isolated rat heart mitochondria	5 µg/mL	5 min	[119]
			Atenolol	Cardiotoxicity	4.99 μM	Isolated rat heart mitochondria	10 µg/mL	5 min	[119]
mPTP	Loss of cytochrome c	Macrolide antibiotics	Azithromycin	Arrhythmia	0.32–0.87 μM	Isolated rat heart mitochondria	50 μM		[120]
			Clarithromycin	TdP	2.67–13.37 μM	Isolated rat heart mitochondria	50 μM		[120]
			Erythromycin	TdP	11 μM	Isolated rat heart mitochondria	50 μM		[120]
mPTP	Loss of cytochrome c	Diabetes medication	Pioglitazone	HF	2.6 μM	Isolated rat heart mitochondria	12.5 µg/mL		[122]

Abbreviations: OXPHOS: oxidative phosphorylation; MMP: mitochondrial membrane potential; mPTP: mitochondrial permeability transition pore; NRTIs: nucleoside reverse transcriptase inhibitors; NSAIDs: nonsteroidal anti-inflammatory drugs; TKIs: tyrosine kinase inhibitors; DOX: doxorubicin; LVEF: left ventricular ejection fraction; HF: heart failure; LVD: left ventricular dysfunction; TdP: torsades de pointes; CHF: congestive hearts failure; MI: myocardial infarction; AF: atrial fibrillation; CMP: cardiomyopathy; VF: ventricular fibrillation; CA: cardiac arrest; CI: cardiac ischemia; ST: sinus tachycardia; HMC: hemorrhagic myocarditis; SBC: sinus bradycardia; ECA: electrocardiographic alterations; VA: ventricular arrhythmia; HA: heart attack; IP: intraperitoneal; IV: intravenously; SC: subcutaneously; BID: twice daily; w: week; d: day; h: hours.