Dose, duration and mode of administration of hormones influence breast cancer risk

Lakshmanaswamy, Rajkumar

doi:10.1016/j.ddmec.2012.10.001

Drug Discovery Today: Disease Mechanisms

2012

DOI: 10.1016/j.ddmec.2012.10.001

|View full text |Cite

Dose, duration and mode of administration of hormones influence breast cancer risk

Rajkumar Lakshmanaswamy

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2012

2013

Publication Types

Select...

Article2

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

(1 citation statement)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rajkumar has investigated the effects of dose, duration and route of administration on breast cancer risk associated with use of hormone replacement therapy (HT) in postmenopausal women [3]. Overall, studies to date are insufficient to support the conclusion that differences in breast cancer risk can be achieved by changing the dosage, duration or route of administration of HT.…”

mentioning

confidence: 99%

Preface

Cavalieri

Rogan

2012

Drug Discovery Today: Disease Mechanisms

View full text Add to dashboard Cite

mentioning

confidence: 99%

Preface

Cavalieri

Rogan

2012

Drug Discovery Today: Disease Mechanisms

View full text Add to dashboard Cite

Pharmacological characterization of N1-(2-methoxyphenyl)-N4-hexylpiperazine as a multi-target antagonist of α1A/α1D-adrenoceptors and 5-HT1A receptors that blocks prostate contraction and cell growth

Chagas-Silva

Nascimento-Viana

Romeiro

et al. 2013

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Benign prostatic hyperplasia (BPH) is a progressive disease related to the imbalance of cell growth and apoptosis, and it plays a key role in the development of lower urinary tract symptoms (LUTS). The main pharmacological treatment is based on α1A-adrenoceptor blockers, but in several cases monotherapy has failed. Recent studies of prostate pathophysiology have noted the role of α1D-adrenoceptors and 5-HT1A receptors in prostate cell proliferation in addition to the usual role of α1A-adrenoceptors in prostate contraction. N-phenylpiperazine is a scaffold structure that may confer drug affinity for these three receptors. Therefore, the present work aimed to investigate the pharmacological characteristics of N1-(2-methoxyphenyl)-N4-hexylpiperazine (LDT66). Using isometric contraction assays with rat prostate and aorta, LDT66 reduced phenylephrine-induced contractions and showed K B values of 3.4 and 2.2 nM for α1A- and α1D-adrenoceptors, respectively. According to the functional binding assays data, LDT66 showed a high affinity (nanomolar range) for the 5-HT1A receptors, behaving as an antagonist. LDT66 also showed a low affinity (micromolar range) for receptors unrelated to BPH such as α1B-adrenoceptors, α2A-adrenoceptors, muscarinic and 5-HT2A receptors, which is a desirable profile in order to prevent putative side effects. Accordingly, LDT66 (100 μg/kg) showed a marginal hypotensive effect. Using the DU-145 prostate cells, control experiments characterized the α1D-adrenoceptor- and 5-HT1A receptor-mediated cell growth by phenylephrine and 5-HT, respectively. LDT66 (50 nM) prevented both effects similarly. In conclusion, LDT66 is a high-affinity multi-target antagonist of relevant receptors for BPH, and it may be a new starting point for multi-target drug development to treat BPH and LUTS.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Dose, duration and mode of administration of hormones influence breast cancer risk

Cited by 2 publications

References 56 publications

Preface

Preface

Pharmacological characterization of N1-(2-methoxyphenyl)-N4-hexylpiperazine as a multi-target antagonist of α1A/α1D-adrenoceptors and 5-HT1A receptors that blocks prostate contraction and cell growth

Contact Info

Product

Resources

About