5-HT1A-agonistic properties of naftopidil, a novel antihypertensive drug

Borbe, Harald O.; Metzenauer, P.; Szelenyi, Istvan

doi:10.1016/0014-2999(91)90779-p

Cited by 17 publications

(5 citation statements)

References 3 publications

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“…Based on binding assays, LDT3 and LDT5 have high affinity for 5-HT 1A receptors (Table 3). Importantly, LDT3 and LDT5 showed higher affinity for 5-HT 1A receptors than LDT66 (ChagasSilva et al, 2014) and naftopidil, another N-phenylpiperazine compound (K i 5 107 nM; Borbe et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

New Multi-target Antagonists of 1A-, 1D-Adrenoceptors and 5-HT1A Receptors Reduce Human Hyperplastic Prostate Cell Growth and the Increase of Intraurethral Pressure

Nascimento-Viana

Carvalho

Nasciutti

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Benign prostatic hyperplasia (BPH) is characterized by stromal cell proliferation and contraction of the periurethral smooth muscle, causing lower urinary tract symptoms. Current BPH treatment, based on monotherapy with a 1A -adrenoceptor antagonists, is helpful for many patients, but insufficient for others, and recent reports suggest that stimulation of a 1D -adrenoceptors and 5-hydroxytryptamine (serotonin) (5-HT) 1A receptors contributes to cell proliferation. In this study, we investigated the potential of three N-phenylpiperazine derivatives (LDT3, LDT5, and LDT8) as multi-target antagonists of BPH-associated receptors. The affinity and efficacy of LDTs were estimated in isometric contraction and competition-binding assays using tissues (prostate and aorta) and brain membrane samples enriched in specific on-or off-target receptors. LDTs' potency was estimated in intracellular Ca 21 elevation assays using cells overexpressing human a 1 -adrenoceptor subtypes. The antiproliferative effect of LDTs on prostate cells from BPH patients was evaluated by viable cell counting and 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays. We also determined LDTs' effects on rat intraurethral and arterial pressure. LDT3 and LDT5 are potent antagonists of a 1A -, a 1D -adrenoceptors, and 5-HT 1A receptors (K i values in the nanomolar range), and fully inhibited phenylephrine-and 5-HT-induced proliferation of BPH cells. In vivo, LDT3 and LDT5 fully blocked the increase of intraurethral pressure (IUP) induced by phenylephrine at doses (ED 50 of 0.15 and 0.09 mg.kg 21 , respectively) without effect on basal mean blood pressure. LDT3 and LDT5 are multi-target antagonists of key receptors in BPH, and are capable of triggering both prostate muscle relaxation and human hyperplastic prostate cell growth inhibition in vitro. Thus, LDT3 and LDT5 represent potential new lead compounds for BPH treatment.

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Section: Discussionmentioning

confidence: 99%

New Multi-target Antagonists of 1A-, 1D-Adrenoceptors and 5-HT1A Receptors Reduce Human Hyperplastic Prostate Cell Growth and the Increase of Intraurethral Pressure

Nascimento-Viana

Carvalho

Nasciutti

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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“…Although it is known that orally administrated naftopidil rapidly distributes to the rat brain [13] and naftopidil has affinity for 5-HT 1A receptors comparable to that for ␣ 1 -adrenoceptors [14] , the central effect of naftopidil may be milder than that of tamsulosin since a different ␣ 1 -blocker has differential affinity for dopamine and 5-HT 1A receptors [12] . Headto-head comparison of affinity for these receptors among several ␣ 1 -blockers is necessary because the available information is extremely limited.…”

Section: Discussionmentioning

confidence: 99%

Ejaculatory Disorders Caused by Alpha-1 Blockers for Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Comparison of Naftopidil and Tamsulosin in a Randomized Multicenter Study

Masumori

Tsukamoto²,

Iwasawa³

et al. 2009

Urol Int

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Introduction: To investigate the incidence of ejaculatory disorders caused by naftopidil and tamsulosin in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Materials and Methods: Ninety-five patients with LUTS/BPH who had International Prostate Symptom Scores (IPSS) of 8 or more were randomly assigned to receive naftopidil (50 mg/day, n = 48) or tamsulosin (0.2 mg/day, n = 47). Before and 12 weeks after treatment, a questionnaire was used to evaluate ejaculation. Results: Among men who had sexual activity during the 12 weeks, the proportion who reported an abnormal feeling on ejaculation was higher in the tamsulosin group (16.7%) than in the naftopidil group (7.4%), although the difference was not significant (p = 0.402). The proportion of men who reported reduced ejaculatory volume after treatment was significantly higher in the tamsulosin group (96.0%) than in the naftopidil group (73.1%, p = 0.0496). On the other hand, the improvements in IPSS and the quality of life index were significantly higher in the tamsulosin group than in the naftopidil group. Conclusions: Tamsulosin may cause a higher incidence of ejaculatory disorders than naftopidil, although the efficacy of 0.2 mg tamsulosin may be better than that of 50 mg naftopidil.

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“…Thus, the presence of pharmacologically active metabolites could contribute to the in vivo duration of action of the parent compound, naftopidil. Preliminary investigations on the affinity of naftopidil to either native (rat tissue) or cloned (COS cells) a -adrenoceptor subtypes indicate no subtype selectivity (pK, values: Furthermore, a high affinity of naftopidil to 5-HTlA receptors and a stimulation of 5-HT,, receptors with subsequent decrease in blood pressure in cats could be demonstrated (3,38). This finding is particularly important for two reasons.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Naftopidil, A Novel Antihypertensive Drug

Himmel

1994

Cardiovascular Drug Reviews

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5-HT1A-agonistic properties of naftopidil, a novel antihypertensive drug

Cited by 17 publications

References 3 publications

New Multi-target Antagonists of 1A-, 1D-Adrenoceptors and 5-HT1A Receptors Reduce Human Hyperplastic Prostate Cell Growth and the Increase of Intraurethral Pressure

New Multi-target Antagonists of 1A-, 1D-Adrenoceptors and 5-HT1A Receptors Reduce Human Hyperplastic Prostate Cell Growth and the Increase of Intraurethral Pressure

Ejaculatory Disorders Caused by Alpha-1 Blockers for Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Comparison of Naftopidil and Tamsulosin in a Randomized Multicenter Study

Naftopidil, A Novel Antihypertensive Drug

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