I don't think anyone has mentioned the issue of sight regulation. Several years ago, I loaded up some 300 gr. loads for my Mountain Gun to take along with me to bear country. With the rear sight bottomed out, it still shot about about 4" high at 25 yards. When you go heavier than 300 grains, you stand a good chance of running out of sight adjustment in most any handgun, especially with longer barrels.
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