Over 450 patients have used Z160 without severe consequences (side effects)
Dr. Corrigan has not seen the results of either Z160 trial yet, but he has been closely following the safety data. He has reviewed the safety data of over 450 patients, and he stressed in his talk that no severe consequences (side effects) so far. This is great news!
He did not, however, say that there have been no side effects because, as with any drug, some side effects have been report, just not severe ones.
Now, think about Z160 for a moment. It is a highly specific N-type (Cav 2.2) calcium channel blocker with 'state dependence'. This means that it binds Cav 2.2 calcium channels only when they are in a conformation that occurs during pain. As a result, Z160 is 'target specific'. This is good because it does not target other channels that have important roles in the nervous system.
So, what are these mild side effects that patients are reporting? Mild drowsiness or weakness perhaps? Diarrhea, constipation, or loss of appetite perhaps? Who knows! Some of these reported side effects likely have nothing to do with Z160, but remember, the trial is placebo controlled, so Dr. Corrigan has most likely spotted some real, although minor, side effects in unblinded safety data. Remember the study design is: Randomized, Double-Blind, Placebo-Controlled.
Now, during his talk, Dr. Corrigan said, 'without severe consequences', and by severe, he means any side effect that would halt the study. He also gave the impression that the side effects in general are not a problem.
But, as all drug usually have side effects, they are also often associated with drug activity. If there is anything to glean from Z160's minor side effects at this juncture, it is that Z160 almost certainly has sufficient bioavailability to hit its target, and it is blocking channels and most likely pain. So, minor side effects are a big HINT, HINT, HINT that Z160 is doing its thing.
This is very important. This means it is targeting the correct area, and think of it like this. Prialt, which is already a FDA approved drug and in the market, does essentially the same thing as Z160 but has side effects.
If Prialt is approved, and that drug essentially validates the work at Z, then Z160 is looking pretty good. State dependence is the key here. The animal models thus far has shown that Z160 is heading in the right direction, but unlike Prialt has little side effects.
Z160 is very target specific, but it is causing some minor side effects (as I read between Dr. Corrigan's lines), probably as a result of hitting its target.
So, Z160 does appear to be on target, enough so that it is causing some minor disturbance in the force (so to speak). Beyond impeding pain signaling, which is what we want, it naturally is going to cause some minor side effects, which can be dealt with by tweaking the dose.
I do not think the molecule is off target though, its too specific. The minor side effects alluded to by Dr. Corrigan are likely a consequence of calcium channel blocking on target. Nothing major though, we know this much based on what Dr. Corrigan said.
The original NMED160 had no side effects at large doses because it had low bioavailability. Z160 has dramatically increased bioavailability, so we are seeing the minor side effects noticed in only high-dose NMED160. Regardless, so far so good. Whatever these side effects are that are being reported, they are not significant, but do suggest Z160 activity, and because of specificity, you can bet it is active on target.
As for water lacking side effects, if you drink enough water, it can cause hyponatremia and death. A fraternity dare some years ago to drink enormous quantities of water killed a university student. Its all about dose, be it water or Z160.