Medical management of benign prostatic hyperplasia: a canine model comparing the in vivo efficacy of alpha-1 adrenergic antagonists in the prostate.
Medical management of benign prostatic hyperplasia (BPH) is an alternative to surgical treatment of this disease. A major target for pharmacologic therapy is the alpha-1 adrenergic receptor, since activation of this receptor by endogenous catecholamines is thought to contribute to outlet obstruction. In the present study, we compared the potency of various alpha-1 adrenergic antagonists against epinephrine-induced contraction of the canine prostate. The drugs tested were dibenzyline, prazosin, terazosin and YM617. The rank order of potency, comparing inhibitory constants (Ki's), was found to be YM617 >> prazosin > terazosin > dibenzyline. This study is the first to compare all of these drugs directly in the prostate in vivo. The rank order of potency of the drugs is similar to the rank order of potency at other alpha-1 receptors. These results demonstrate that 1) our model is useful in confirming activity of drugs at the alpha-1 receptor and 2) the prostate alpha-1 receptor is similar to other alpha-1 receptors. Whether activity at the alpha-1 adrenergic receptor is a sufficient determinant of clinical efficacy of these drugs remains to be determined.
Breslin
D
D
Department of Surgery/Division of Urology, New York Hospital-Cornell Medical Center, New York 10021.
Fields
D W
DW
Chou
T C
TC
Marion
D N
DN
Kane
M
M
Vaughan
E D
ED
Felsen
D
D
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010643:Phenoxybenzamine / Q000494:pharmacology / Q000627:therapeutic use*; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D011467:Prostate / Q000187:drug effects* / Q000502:physiology; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D000077409:Tamsulosin
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D013449:Sulfonamides; D010643:Phenoxybenzamine; C041226:Terazosin; D000077409:Tamsulosin; D011224:Prazosin; D004837:Epinephrine