the blood runs more freely. alpha-1 blockers have a good effect on lipoproteins in plasma, insulin resistance and it causes the glucose levels in blood to lower. structure activity relationship (sar) by changing the furan ring in prazosin to tetrahydrofuran ring (as in alfuzosin) the half-life is greatly increased, allowing once-a-day dosing. silodosin is the most selective for alpha-1a receptors. the affinity and selectivity for alpha-1 receptors seems to be determined by structure between the quinazoline and the furan ring. piperazine is present in prazosin, terazosin and doxazosin which seems to contribute to the non-selective inhibition of alpha-1 receptors. comparison between prazosin, terazosin, and alfuzosin. the conversion of the furan ring to a tetrahydrofuran ring (colored purple) contributed to an increase in half-life of terazosin. the conversion of piperazine to aminopropyl (colored red) increases the selectivity for alpha-1a receptors. doxazosin 2,4-diamino-6,7-dimethoxyquinazoline variations for in vitro and in vivo performance. a key factor in these structures were the derivations from 2,4-diamino-6,7-dimethoxyquinazoline nucleus that was replaced for norepinephrine. and n-1 which protonated quinazoline was also a key factor. variation of structure 2,4-diamino-6,7-dimethoxyquinazoline., where x = ch, n tamsulosin is most potent alpha 1 blocker and has the most selectivity for alpha 1a receptors. it has no beta-blocking activity. history the first effective treatment for benign prostatic hyperplasia (bph) was a non-selective alpha blocker phenoxybenzamine which was irreversible. dibenzyline was the first brand name marketed. today phenoxybenzamine is not the first choice due to many side effects like lowering blood pressure. first selective alpha-1 blocker that was approved to treat hypertension was prazosin. prazosin was synthesized in 1974 when constantin and hess were trying to discover a vasodilator which had a minimal effect on cardiac activity. prazosin was a much better tolerated drug than phenoxybenzamine but the problem still remained that it lowered the blood pressure more than desired for a bph treatment. terazosin was the first long-lasting alpha 1 blocker approved by fda to treat bph. doxazosin and tamsulosin were approved after. the first-line treatment choice today to treat bph is tamsulosin. it is not better tolerated, nor does it have greater efficacy than the previous drugs, however, it requires minimal dose titration in comparison. alfuzosin sr (sustained release) was the fourth alpha 1 selective blocker to be approved by fda and requires no dose titration.