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Medicinal Research Reviews Sep 2015Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable "Renaissance drug" worthy of commemoration. Perhaps the... (Review)
Review
Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable "Renaissance drug" worthy of commemoration. Perhaps the only facet of noscapine's profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum. This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine's purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine's unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino-noscapine, 9-nitronoscapine, 9-bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds.
Topics: Alkaloids; Animals; Antineoplastic Agents; Centrosome; Chemistry, Pharmaceutical; Drug Evaluation, Preclinical; Female; Humans; Male; Microtubules; Neoplasms; Noscapine; Papaver; Plant Extracts; Stroke; Warfarin
PubMed: 26179481
DOI: 10.1002/med.21357 -
Nature Communications Oct 2022The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms...
The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAc) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAc) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAc neurons impairs reward seeking behavior, while silencing of NAc or NAc→LH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion.
Topics: Mice; Animals; Nucleus Accumbens; Reward; Ventral Tegmental Area; Dopaminergic Neurons; Opiate Alkaloids
PubMed: 36271048
DOI: 10.1038/s41467-022-33843-3 -
Shock (Augusta, Ga.) Sep 1999The presence of opiate receptors in mammalian tissues has stimulated the search for endogenous ligands to these receptors and has led to the discovery and... (Review)
Review
The presence of opiate receptors in mammalian tissues has stimulated the search for endogenous ligands to these receptors and has led to the discovery and characterization of endogenous opioid peptides. However, recent studies have provided evidence for the presence of opiate alkaloids in mammalian tissues and for their endogenous synthesis. The study of their origin and synthetic pathway has been significantly influenced by the early classical biochemical studies performed in plants. This review is a historical account of the use and abuse of opiates, the elucidation of morphine's synthetic pathway in the poppy plant, and the subsequent characterization of its presence in mammalian tissues. Clearly, our understanding of its synthetic pathway and regulation is a reflection of observations originally made in plant biochemistry.
Topics: Alkaloids; Analgesics, Opioid; Animals; Humans; Morphine; Opioid-Related Disorders; Opium; Plants; Receptors, Opioid
PubMed: 10485593
DOI: No ID Found -
Revue Medicale Suisse Aug 2023
Topics: Humans; Opiate Alkaloids; Low Back Pain; Neck Pain; Acute Pain
PubMed: 37610198
DOI: 10.53738/REVMED.2023.19.838.1530 -
Revue Medicale Suisse Oct 2023
Topics: Humans; Opiate Alkaloids; Neck Pain
PubMed: 37850812
DOI: 10.53738/REVMED.2023.19.846.1959 -
World Journal of Surgery Apr 2022The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown.
OBJECTIVE
The present systematic review and meta-analysis aims to compare the efficacy of different analgesic modalities trialled in AP.
METHODS
A systematic search of PubMed, MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science conducted up until June 2021, identified all randomised control trials (RCTs) comparing analgesic modalities in AP. A pooled analysis was undertaken of the improvement in pain scores as reported on visual analogue scale (VAS) on day 0, day 1 and day 2.
RESULTS
Twelve RCTs were identified including 542 patients. Seven trial drugs were compared: opiates, non-steroidal anti-inflammatories (NSAIDs), metamizole, local anaesthetic, epidural, paracetamol, and placebo. Across all modalities, the pooled VAS scores showed global improvement from baseline to day 2. Epidural analgesia appears to provide the greatest improvement in VAS within the first 24 h but is equivalent to opiates by 48 h. Within 24 h, NSAIDs offered similar pain-relief to opiates, while placebo also showed equivalence to other modalities but then plateaued. Local anaesthetics demonstrated least overall efficacy. VAS scores for opiate and non-opiate analgesics were comparable at baseline and day 1. The identified RCTs demonstrated significant statistical and methodological heterogeneity in pain-relief reporting.
CONCLUSIONS
There is remarkable paucity of level 1 evidence to guide pain management in AP with small datasets per study. Epidural administration appears effective within the first 24 h of AP although infrequently used and featured in only a single RCT. NSAIDs are an effective opiate sparing alternative during the first 24 h.
Topics: Analgesia; Analgesics; Analgesics, Opioid; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Humans; Opiate Alkaloids; Pain; Pain Management; Pancreatitis; Randomized Controlled Trials as Topic
PubMed: 34994837
DOI: 10.1007/s00268-021-06420-w -
American Journal of Rhinology & Allergy May 2022The literature on opiate use after endoscopic endonasal transsphenoidal surgery (EETS) is limited.
BACKGROUND
The literature on opiate use after endoscopic endonasal transsphenoidal surgery (EETS) is limited.
OBJECTIVE
To determine the risk factors for higher opiate use following EETS and the quantity of opiates used after discharge.
METHODS
A retrospective review of 144 patients undergoing EETS from July 2018 to July 2020 was conducted. Patient, tumor, and surgical factors were documented. Pain scores and medications used on postoperative days (POD) 0 and 1, and discharge prescriptions, were recorded. Opiate use was quantified using morphine milligram equivalents (MME) dose. Multiple linear regression determined risk factors independently associated with POD0 to 1 opiate use.
RESULTS
On POD 0 to 1, mean pain score was 4.9/10 (standard deviation [SD] ± 2.0). Mean acetaminophen use was 3.4 tablets (SD ± 1.6; 650 mg per tablet). Mean opiate use was 35.6 MME (SD ± 36.3), equivalent to 4.7 tablets (SD ± 4.8) of oxycodone 5 mg. Multiple linear regression showed that current smokers required an additional 37.1 MME ( = .011), and patients with grade 3 intraoperative cerebrospinal fluid leaks required an additional 36.7 MME ( = .046) on POD0 to 1. On discharge, mean opiate prescription was 117.7 MME (SD ± 102.1), equivalent to 15.7 tablets (SD ± 13.6) of oxycodone 5 mg. Thirty-nine patients (27.1%) did not require prescriptions. Only 10 patients (6.9%) required opiate refill(s) within 30 days after surgery.
CONCLUSION
Patients undergoing EETS have higher opiate needs compared to those undergoing endoscopic sinus surgery, although the overall requirements are still considered low. Independent risk factors associated with higher opiate use in the immediate postoperative period included current smokers and grade 3 intraoperative cerebrospinal fluid leaks.
Topics: Analgesics, Opioid; Cerebrospinal Fluid Leak; Endoscopy; Humans; Opiate Alkaloids; Pain, Postoperative; Retrospective Studies
PubMed: 34881667
DOI: 10.1177/19458924211061990 -
BMJ (Clinical Research Ed.) Feb 2023
Topics: Humans; Opiate Alkaloids; Opioid-Related Disorders; Self Efficacy; Personal Autonomy
PubMed: 36805854
DOI: 10.1136/bmj.p400 -
Nature Nov 2017
Topics: Analgesics, Opioid; Death; Humans; Opiate Alkaloids; Opioid-Related Disorders
PubMed: 29189802
DOI: 10.1038/d41586-017-07657-z -
Revue Medicale Suisse Jan 2024
Topics: Humans; Opiate Alkaloids; Pain Management
PubMed: 38268354
DOI: 10.53738/REVMED.2024.20.858.130