Using Verapamil alone resulted in a 10-fold inhibition and papaverine resulted in 18-fold inhibition of CMV but combined the inhibition was 112-fold inhibition....
Seth starting swallowing Verapamil and Papaverine.
Ok I'm done. The link is below
Abstract
The disclosure demonstrates the inhibition of replication of human cytomegalovirus (HCMV) in cultured human embryo skin muscle cells by two separate subclasses of direct-acting smooth muscle relaxing agents alone or in combination with each other. These two subclasses are characterized mechanistically as calcium influx blockers (or calcium channel blockers) and cyclic nucleotide modulators. More specifically, the class of calcium influx blockers is exemplified by the drugs verapamil (and methoxyverapamil), nifedipine (the prototype drug of 1,4 dihydropyridines), and diltiazem. The class of cyclic nucleotide modulators is exemplified by the drugs isobutylmethylxanthine, papaverine (and its synthetic analog dioxyline), forskolin, and sodium nitroprusside. In addition, the present disclosure demonstrates that agents from one class, e.g., a calcium influx blocker, act synergistically when used in combination with agents from the other class, e.g., cyclic nucleotide modulators. The calcium influx blockers are shown to act synergistically when used in combination with alpha interferon. In further embodiments, papaverine family member agents are shown to exert antiviral activity synergistically with antiviral nucleoside analogs.
So I am wondering if it is hard to get that papaverine and how would it mix with other drugs in the cocktail.
ReplyDeleteAlthough I don't dispute that verapamil has potential benefits for brain tumors, in vitro studies always need to be closely scrutinized, particularly with respect to drug concentrations used. In this study, verapamil concentrations of 15 - 30 ug/ml were used (or 33 - 66 micromolar) and 15 micromolar gave a 50% inhibition of HCV.
ReplyDeleteMaximum plasma concentrations of verapamil in humans with high standard dosing is about 0.6 micromolar, but 90% of this is bound to plasma proteins, giving an effective maximal concentration of about 0.06 micromolar (60 nM).
In other words, the lowest concentrations used in this study are about 250 times higher than maximal effective concentrations in human plasma with standard dosing.
oh :( that's why I need your input
ReplyDeleteWe are starting Verapamil anyway. There were few people in this group who did not take verapamil because we took sertraline and tumors progressed. So we are giving it a try.
ReplyDeleteI hope my statements aren't understood as saying people shouldn't take verapamil. Rather, I'm pointing out that drugs do a lot of things in vitro that they'll never do in vivo, because of the excessive concentrations used in vitro.
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