Does a Bleeding Disorder Lessen the Efficacy of the 52-mg Levonorgestrel-Releasing Intrauterine System for Heavy Menstrual Bleeding in Adolescents? A Retrospective Multicenter Study.

Purpose: The aim of this study is to compare the patient-reported bleeding outcomes and complication rates with the use of the 52-mg levonorgestrel-releasing intrauterine system (52-LNG-IUS) for treatment of heavy menstrual bleeding (HMB) among adolescents with and without a diagnosed inherited bleeding disorder (BD) within the first 12 months after insertion.

Methods: Retrospective chart review was conducted of adolescents ages 14-21 years, with and without an inherited BD, who underwent 52-LNG-IUS insertion between September 2013 and February 2020 for the treatment of HMB.

Results: One hundred forty-four 52-LNG-IUS insertions among 139 subjects were evaluated.

Probes for narcotic receptor mediated phenomena 49. N-substituted rac-cis-4a-arylalkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.

Racemic N-substituted -1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols containing cis-4a-aralkyl groups were explored as probes for opioid receptors. Specifically cis-4a-phenylpropyl, -phenylbutyl, and-phenylpentyl groups coupled with widely varied substituents on the nitrogen atom were synthesized and their pharmacological profiles at opioid receptors examined. The study yielded compounds with good affinity and moderate to potent antagonist activity at the μ- and δ-opioid receptors, and agonist activity at the κ-opioid receptor.

Effect of Iboga alkaloids on µ-opioid receptor-coupled G protein activation.

Objective: The iboga alkaloids are a class of small molecules defined structurally on the basis of a common ibogamine skeleton, some of which modify opioid withdrawal and drug self-administration in humans and preclinical models. These compounds may represent an innovative approach to neurobiological investigation and development of addiction pharmacotherapy. In particular, the use of the prototypic iboga alkaloid ibogaine for opioid detoxification in humans raises the question of whether its effect is mediated by an opioid agonist action, or if it represents alternative and possibly novel mechanism of action.

Probes for narcotic receptor mediated phenomena. 48. C7- and C8-substituted 5-phenylmorphan opioids from diastereoselective alkylation.

The exploration of the effect of substituents at C7 and C8 of the 5-phenylmorphans on their affinity for opioid receptors was enabled by our recently introduced "one pot" diastereoselective synthesis that provided C7-oxo, hydroxy and alkyl substituents, C8-alkyl substituted 5-phenylmorphans, and compounds that had a new cyclohexane ring that includes the C7 and C8 carbon atoms of the 5-phenylmorphan. The affinity of the 5-phenylmorphans for opioid receptors is increased by a C8-methyl substituent, compared with its C7 analog. The affinity of the newly synthesized compounds is generally for the μ-opioid receptor, rather than the δ- or κ-receptors.

Probes for narcotic receptor mediated phenomena. 47. Novel C4a- and N-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.

A series of N-methyl rac-cis-4a-aralkyl- and alkyl-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols have been prepared (2a-l) using a simple previously designed synthetic route, in order to find a ligand that would interact with both μ- and δ-opioid receptors. A C4a-phenethyl derivative 2a, was found to have modest receptor affinity both at μ- (K(i)=60 nM) and δ-opioid receptors (K(i)=64 nM). The N-methyl substituent of 2a and that of other ligands in the series was then modified to obtain compounds with different N-substituents that might provide higher affinity at both receptors.