Classics in Chemical Neuroscience: Buprenorphine

Abstract

Buprenorphine has not only had an interdisciplinary impact on our understanding of key neuroscience topics like opioid pharmacology, pain signaling, and reward processing but has also been a key influence in changing the way that substance use disorders are approached in modern medical systems. From its leading role in expanding outpatient treatment of opioid use disorders to its continued influence on research into next-generation analgesics, buprenorphine has been a continuous player in the ever-evolving societal perception of opioids and substance use disorder. To provide a multifaceted account on the enormous diversity of areas where this molecule has made an impact, this article discusses buprenorphine's chemical properties, synthesis and development, pharmacology, adverse effects, manufacturing information, and historical place in the field of chemical neuroscience.

Alkaloids in Contemporary Drug Discovery to Meet Global Disease Needs

“…Morphine, atropine, cocaine, aconitine, penicillin, cephalosporin, vinblastine, and camptothecin have each served in the past as alkaloid scaffolds for modification to improve potency, diversify their applications, or reduce toxicity [2]. Hundreds of derivatives have been synthesized based on the original alkaloids, and some products, particularly in the morphine alkaloid [183][184][185] and the cephalosporin and penicillin [186,187] series, have become important drugs.…”

Patient-Reported Outcomes of Treatment of Opioid Dependence With Weekly and Monthly Subcutaneous Depot vs Daily Sublingual Buprenorphine

“…[3][4][5] Buprenorphine is a partial μ-opioid receptor agonist, enabling office-based treatment for nonsupervised or take-home use of the medication. 6,7 However, SL formulations of buprenorphine are prone to nonmedical use (eg, injecting, diversion), prompting models of care, particularly in the early phases of treatment, requiring regular attendance at clinics or pharmacies for administration of doses. 8,9 Long-acting injectable depot buprenorphine formulations have been developed to mitigate some of the concerns of daily dosing.…”

Cross‐Coupling‐Cyclocondensation Reaction Sequence to Access a Library of Ring‐C Bridged Pyrimidino‐tetrahydrothebaines and Pyrimidinotetrahydrooripavines

“…[2] This molecule has made an impact on the understanding of opioid pharmacology, pain signaling, adverse processing and chemical neuroscience. [3] Compound 2, a semisynthetic thebaine/oripavine derivative, belongs structurally to the ring-C bridged 4,5-epoxymorphinans (6,14-ethanomorphinans, orvinols or Bentley-compounds). [1,4] To this group belong also diprenorphine 3, a well known member of the orvinol class of semi-synthetic 4,5-epoxy-morphinans derived from Diels-Alder reactions with thebaine 1 a, first prepared by Bentley 1b .…”

“…[19][20][21] The therapeutic effect of a variety of 2,4,5-and 2,4,6-trisubstituted pyrimidines is mainly attributed to an antagonistic effect to the adenosine receptors A 1 [22] and A 2A . [23] It is well known that morphinans possess diverse pharmacological effects on the central nervous system [3,24] and a low level of endogenous opioids may be protective for neurodegenerative disease. Of interest was the chemical combination of adenosine receptor antagonists with 2-substututed 4-arylpyrimidine framework as a pharmacophore group, and an oripavine-type framework with the known opioid receptor targeted antinociception properties.…”

“…At higher dosage this compound was used for substitution therapy in the management of opiate addiction [2] . This molecule has made an impact on the understanding of opioid pharmacology, pain signaling, adverse processing and chemical neuroscience [3] . Compound 2 , a semisynthetic thebaine/oripavine derivative, belongs structurally to the ring‐C bridged 4,5‐epoxymorphinans (6,14‐ethanomorphinans, orvinols or Bentley‐compounds) [1,4] .…”