Naftopidil

Naftopidil (Flivas), a selective α1-adrenergic receptor antagonist or alpha blocker, is an antihypertensive drug.Target: α1-Adrenergic ReceptorNaftopidil significantly improved the overall international prostatic symptom score ; from 19.2±7.9 to 11.7±5.8 in the M group and from 19.4±6.4 to 12.3±6.8 in the E group (p<0.0001), QOL score from 4.9±0.8 to 3.2±1.4 in the M group and from 5.0±0.8 to 3.6±1.3 in the E group (p<0.0001), and OAB symptom score from 7.8±2.6 to 5.0±2.5 in the M group (p<0.0001) and from 8.6±2.9 to 5.8± 3.3 in the E group (p<0.0001). naftopidil improves storage symptoms as well as voiding symptoms regardless of timing of administration [1]. The selectivity of naftopidil for prostatic pressure was the most potent among the test compounds. In addition, using cloned human alpha1-adrenoceptor subtypes, naftopidil was selective for the alpha1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha1a- and alpha1b-adrenoceptor subtypes, respectively. The selectivity of naftopidil for prostatic pressure may be attributable to its high binding affinity for alpha1a- and alpha1d-adrenoceptor subtypes [2].

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Research Areas >> Cardiovascular Disease

[1]. Sakai, H., et al., [Efficacy of naftopidil in patients with overactive bladder associated with benign prostatic hyperplasia: prospective randomized controlled study to compare differences in efficacy between morning and evening medication]. Hinyokika Kiyo

[2]. Takei, R., et al., Naftopidil, a novel alpha1-adrenoceptor antagonist, displays selective inhibition of canine prostatic pressure and high affinity binding to cloned human alpha1-adrenoceptors. Jpn J Pharmacol, 1999. 79(4): p. 447-54.

Isoprenaline hydrochloride | ICI 118,551 (hydrochloride) | Phenylephrine hydrochloride | Yohimbine hydrochloride | Adrenaline | Ivabradine hydrochloride | Prazosin hydrochloride | Clenbuterol hydrochloride | Phentolamine mesilate | guanfacine hydrochloride | pimozide | Sotalol hydrochloride | Carvedilol | Atenolol | Metroprolol succinate

DATA ITEMS CITED :

4

MOLECULAR FORMULA :

C24-H28-N2-O3

MOLECULAR WEIGHT :

392.54

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4320 mg/kg

SEX/DURATION :

female 16 day(s) after conception - 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 48,7,1994

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1080 mg/kg

SEX/DURATION :

female 16 day(s) after conception - 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 48,7,1994

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

15680 mg/kg

SEX/DURATION :

male 9 week(s) pre-mating female 2 week(s) pre-mating - 3 week(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 48,17,1994

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1300 mg/kg

SEX/DURATION :

female 7-19 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 48,1,1994