n-allylsecoboldine and discretamine

The effects of N-allylsecoboldine, (-)-discretamine, ( )-govadine and [(+/-)-2,3,10,11-tetrahydroxytetrahydroproto-berberine HBr] ((+/-)-THP) on contractile responses were investigated in human hyperplastic prostate. They all inhibited, concentration dependently, the tension responses to phenylephrine and electrical field stimulation, and the pA2 and pIC50 values were calculated. The relative potencies of these four agents with reference to prazosin were obtained. The results showed that N-allylsecoboldine exhibited greater potency (4.1-fold), whereas (-)-discretamine, (+/-)-govadine and (+/-)-THP had similar potencies, against contractions elicited by electrical field stimulation and against contractions elicited by phenylephrine in human hyperplastic prostate. In addition, the potency ratios of N-allylsecoboldine, (-)-discretamine, (+/-)-govadine and (+/-)-THP against phenylephrine-induced contractions in rat vas deferens/spleen were 7.78, 0.89, 0.57, and 0.96, respectively. In the presence of prazosin (0.3 +/-M) to block alpha1-adrenoceptor-mediated responses, nifedipine (10 microM), but not the above four agents, significantly blocked KCl (60 mM)-induced tension responses in human hyperplastic prostate. It is suggested that N-allylsecoboldine exhibits greater potency against nerve-mediated contraction than against phenylephrine-induced contraction in human hyperplastic prostate and that this antagonistic effect is due mainly to its high affinity for the alpha1A-adrenoceptor subtype.

Topics: Adrenergic alpha-Antagonists; Aged; Aged, 80 and over; Alkaloids; Animals; Aporphines; Berberine; Berberine Alkaloids; Calcium; Dose-Response Relationship, Drug; Electric Stimulation; Humans; In Vitro Techniques; Male; Middle Aged; Muscle Contraction; Nifedipine; Phenylephrine; Potassium; Prostate; Prostatic Hyperplasia; Rats; Rats, Wistar; Spleen; Stereoisomerism; Vas Deferens; Vasodilator Agents