Virtually everybody who uses oral minoxidil gets results but MITIGATING the side effects and avoiding tolerance are the keys to long term usage.
The tolerance effect of minoxidil is due to formation of superoxide radical with nitric oxide and then you get the nasty peroxynitrite. Peroxynitrite formation is thought to be a player in many diseases including met syndrome.
Some have used topical NAC with topical minoxidil and reported better results because superoxide is getting scavenged by NAC which keeps nitric oxide levels high and avoids peroxynitrite. Keep NAC and minoxidil separate if you do this.
Some of the arrhythmia problems are discussed here
taurine was mentioned in the above thread and it works for me at about 4-8 gram/day)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264827/
4. Therapeutic implications
Conventional antiarrhythmic drugs target ion channels and reduce ion currents. Nevertheless, in many cases, the targeted ion channels are already downregulated. The role of ROS in arrhythmogenesis, as outlined above, opens new and potentially safer therapeutic options to treat arrhythmias using antioxidants.
Administration of either GSH or
N-acethylcysteine ______significantly______ reduces reperfusion arrhythmias [
186].
Additionally, altering ratios of GSH/GSSH can affect the ΔΨm and the occurrence of arrhythmias [
113]. ROS-mediated collapses of the ΔΨm is prevented by the addition of exogenous GSH [
187].
Ascorbate (vitamin C) reduces the incidence of atrial pacing-induced peroxynitrite formation as well as postoperative AF [
72].
Vitamin E analogues scavenge free radicals and reduce the incidence of ischemia/reperfusion-induced VF [
188]
. Another synthetic ROS scavenger, 6,6-methylene bis 2,2-dimethyl-4-methane sulphonic acid: Na-1,2-dihydroquinoline (MTDQ-A), significantly reduces the incidence of VF after myocardial infarction following coronary ligation in a dog [
189].
Nevertheless, general antioxidant strategies have not always been successful in antiarrhythmic therapies.
Explanations for the strong association of oxidative stress and arrhythmia but a more qualified success of antioxidant strategies to prevent arrhythmias may be explained by the idea that redox stress is compartmentalized. As we discussed above, mitochondrial oxidative stress contributes to a wide range of damage in cardiac metabolism and ion homeostasis. Therefore, reducing mitochondria oxidative stress could be a more effective anti-oxidant approach. Indeed, several mitochondria-targeted ROS scavengers have been developed and are ripe for study of their potential anti-arrhythmic properties [
112,
114,
190-
192].
Strategies targeting mitochondrial ROS release pathways may be antiarrhythmic [
114,
193]. IMAC inhibitors, DIDS and PK11195, can prevent the cell-wide accumulation of ROS and reversible collapses in the ΔΨm [
114,
193]. Furthermore, 4′chlorodiazepam, a mitochondrial benzodiazepine receptor modulator, can prevent reperfusion arrhythmias in isolated rabbit heart [
112]. This inhibitor, as well as DIDS and PK11195, can prevent the
INa decrease induced by elevated NADH and ROS [
16]. Additionally, other mitochondrial targeted antioxidants such as peptides, SS-02 (Dmt-D-Arg-Phe-Lys-NH2), SS-31 (D-Arg-Dmt-Lys-Phe-NH2) and SS-20 (Phe-D-Arg-Phe-Lys-NH2) are also effective in ischemia-reperfusion [
194,
195]. Arrhythmias were significantly reduced in ischemia-reperfusion injured rat hearts when treated SS-02 and SS-31 directly before reperfusion [
196,
197].
The mitochondrial anti-oxidant, MitoQ, is targeted to the mitochondria by covalent conjugation with a lipophilic triphenylphosphonium cation. As previously discussed, CoQ (ubiquinone) accepts electrons from complex I or II, and donates to complex II by the formation of reduced product, ubiquinol [
191]. The protective effects of MitoQ have been demonstrated by the administration to rats in their drinking water [
191]. Under ischemia-reperfusion injury, MitoQ shows significant protection against heart dysfunction, tissue damage, and mitochondrial dysfunction [
191]
. A similar study also has shown that MitoQ has the protective effects on cardiac ischemia-reperfusion injury [
190]. MitoQ shows a protective effect against an increased blood pressure in a hypertensive rat model, which has mitochondrial oxidative damage in endothelial cells [
192]. Therefore, it is likely to have antiarrhythmic properties.
