Two chemically distinct forms of the drug naftopidil (NAF) are both effective in relieving the symptoms of benign prostatic hyperplasia (BPH), according to a recent study using rats.
The report, “Pharmaceutical evaluation of naftopidil enantiomers: Rat functional assays in vitro and estrogen/androgen induced rat benign prostatic hyperplasia model in vivo,” was published in the European Journal of Pharmacology.
NAF, which is marketed under the brand name Flivas, acts as a selective α1-adrenergic receptor antagonist, also known as an alpha-blocker. It is used for the treatment of BPH and lower urinary tract symptoms, such as frequent need to urinate, difficulty starting to urinate and inability to completely empty the bladder.
α1 adrenergic receptors are found on the surface of smooth muscle cells of blood vessels and regulate smooth muscle contraction. They consist of three highly homologous subtypes, including α1A, α1B, and α1D. NAF has 17-fold higher affinity for α1D adrenergic receptors compared to α1B adrenergic receptors, and threefold higher potency compared to α1A adrenergic receptors.
In the clinic, the drug is used as a so-called “racemate,” which is a mixture of the two chemically distinct forms, called S-NAF and R-NAF; they are each other’s mirror image structurally.
The team of researchers from Guangzhou Medical University, in collaboration with colleagues from South China Agricultural University, compared the differences and similarities between the two chemical forms, as well as the racemate of NAF using a rat model of BPH.
They found that the racemate and the two chemical forms showed similar blocking activity on the α1 receptors. However, one of the two chemical forms, S-NAF, was seen to bind more to α1D/1A adrenergic receptor subtypes compared to R-NAF and the racemate. S-NAF also showed an advantage in decreasing the weight and volume of the prostate compared to R-NAF and racemate NAF. However, no other significant differences were observed between the two chemical forms of the drug, and they all effectively prevented the excessive increase of prostatic tissue in rats by suppressing the increase of the prostatic weight.
The researchers concluded that S-NAF may offer a slight advantage compared to R-NAF, and could be favored for the treatment of BPH. However, they added that a more comprehensive pharmacological evaluation of the different chemical forms of NAF should be undertaken.