Glaucine

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Glaucine
Glaucine.svg
Systematic (IUPAC) name
(S)-5,6,6a,7-tetrahydro-1,2,9,10-tetramethoxy-6-methyl-4H-dibenzo[de,g]quinoline
Clinical data
AHFS/Drugs.com International Drug Names
Legal status
?
Identifiers
CAS number 475-81-0 YesY
5630-11-5
ATC code None
PubChem CID 16754
ChemSpider 15883 N
UNII NU19306XA7 N
KEGG D08014 N
ChEMBL CHEMBL228082 N
NIAID ChemDB 011385
Chemical data
Formula C21H25NO4 
Mol. mass 355.428 g/mol
 N (what is this?)  (verify)

Glaucine is an alkaloid found in several different plant species in the Papaveraceae family such as Glaucium flavum,[1] Glaucium oxylobum and Corydalis yanhusuo,[2][3] and in other plants like Croton lechleri in the family Euphorbiaceae.[4]

It has bronchodilator and antiinflammatory effects, acting as a PDE4 inhibitor and calcium channel blocker,[5] and is used medically as an antitussive in some countries.[6] Glaucine may produce side effects such as sedation, fatigue, and a hallucinogenic effect characterised by colourful visual images,[7][8] and has been detected as a novel psychoactive drug.[9]

Mechanism of action[edit]

Glaucine binds to the benzothiazepine site on L-type Ca2+-channels, thereby blocking calcium ion channels in smooth muscle like the human bronchus. Glaucine has no effect on intracellular calcium stores, but rather, does not allow the entry of Ca2+ after intracellular stores have been depleted.[5] Ca2+ influx is a vital component in the process of muscular contraction, and the blocking of this influx therefore reduces the ability of the muscle to contract.[10] In this way, glaucine can prevent smooth muscle from contracting, allowing it to relax.

Glaucine has also been demonstrated to be a dopamine receptor antagonist, favoring D1 and D1-like receptors.[11][9] It is also a non-competitive selective inhibitor of PDE4 in human bronchial tissue and granulocytes. PDE4 is an isoenzyme that hydrolyzes cyclic AMP to regulate human bronchial tone (along with PDE3). Yet as a PDE4 inhibitor, glaucine possesses very low potency.[5]

Glaucine may function as a psychedelic hallucinogen, given that it contains the phenethylamine structure common to such drugs as 2C-B, DOI, and mescaline.

Clinical use[edit]

It is currently used as an antitussive agent in Romania, Bulgaria, Iceland, Russia and other eastern European countries.[5][9] Bulgarian pharmaceutical company Sopharma sells glaucine in tablet form, where a single dose contains 40 mg and the half-life is indicated to be 6–8 hours. When ingested orally has been shown to increase airway conductance in humans, and has been investigated as a treatment for asthma.[5]

Animal studies demonstrate the ability of glaucine to decrease heart rate and lower blood pressure,[12] presumably by the same mechanism of Ca2+-channel antagonism that it uses to relax bronchial muscle. Studies of the effect of several alkaloids in mice, including glaucine, demonstrate anticonvulsant and antinociceptive properties.[13] In other words; animal studies indicate that glaucine can also act as a pain reliever to a certain extent, although its capacities in this respect appear limited when compared to other analgesics.

Symptoms and recreational use[edit]

Reports of recreational use of glaucine have recently been published, and effects include dissociative-type symptoms; feeling detached and ‘in another world’, as well as nausea, vomiting and dilated pupils. These reports mirror those about the effects of clinical use, which state dissociative-type symptoms as well as lethargy, fatigue, hallucinations.[9][8] Investigation of side effects in a clinical setting also reports that the hallucinatory effects manifest as bright and colorful visualizations. They also report that patients perceive their environments clearly yet feel detached from it; “the patient sees and understands everything and is oriented well enough, but cannot take a clear and adequate action”.[8]

One particular report of recreational use gone awry described the form of distribution as tablets being marketed as a 1-benzylpiperazine (BZP)-free “herbal high” which the patient referred to as “head candy”.[9]

See also[edit]

References[edit]

  1. ^ G.B. Lapa; O.P. Sheichenko; A.G. Serezhechkin and O.N. Tolkachev (August 2004). "HPLC Determination of Glaucine in Yellow Horn Poppy Grass (Glaucium flavum Crantz)". Pharmaceutical Chemistry Journal 38 (1): 441–442. doi:10.1023/B:PHAC.0000048907.58847.c6. ISSN 0091-150X. Retrieved 2009-06-14. "S-(+)-Glaucine (C21H25NO4) is the main alkaloid component in the grass of yellow horn poppy (Glaucium luteum L., syn. Glaucium flavum Crantz) of the Papaveraceae family" 
  2. ^ Xu, XH; Yu, GD; Wang, ZT (2004). "Resource investigation and quality evaluation on wild Corydalis yanhusuo". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 29 (5): 399–401. PMID 15706885. 
  3. ^ Morteza-Semnani, K; Amin, G; Shidfar, MR; Hadizadeh, H; Shafiee, A (2003). "Antifungal activity of the methanolic extract and alkaloids of Glaucium oxylobum". Fitoterapia 74 (5): 493–6. doi:10.1016/s0367-326x(03)00113-8. PMID 12837370. 
  4. ^ Milanowski, DJ; Winter, RE; Elvin-Lewis, MP; Lewis, WH (2002). "Geographic distribution of three alkaloid chemotypes of Croton lechleri". Journal of Natural Products 65 (6): 814–9. doi:10.1021/np000270v. PMID 12088421. 
  5. ^ a b c d e Cortijo, J; Villagrasa, V; Pons, R; Berto, L; Martí-Cabrera, M; Martinez-Losa, M; Domenech, T; Beleta, J; Morcillo, EJ (1999). "Bronchodilator and anti-inflammatory activities of glaucine: In vitro studies in human airway smooth muscle and polymorphonuclear leukocytes". British Journal of Pharmacology 127 (7): 1641–51. doi:10.1038/sj.bjp.0702702. PMC 1566148. PMID 10455321. 
  6. ^ Rühle, KH; Criscuolo, D; Dieterich, HA; Köhler, D; Riedel, G (1984). "Objective evaluation of dextromethorphan and glaucine as antitussive agents". British Journal of Clinical Pharmacology 17 (5): 521–4. doi:10.1111/j.1365-2125.1984.tb02384.x. PMC 1463443. PMID 6375709. 
  7. ^ Rovinskiĭ, VI (1989). "A case of hallucinogen-like action of glaucine". Klinicheskaia meditsina 67 (9): 107–8. PMID 2586025. 
  8. ^ a b c Rovinskiĭ, VI (2006). "Acute glaucine syndrome in the physician's practice: The clinical picture and potential danger". Klinicheskaia meditsina 84 (11): 68–70. PMID 17243616. 
  9. ^ a b c d e Dargan, PI; Button, J; Hawkins, L; Archer, JR; Ovaska, H; Lidder, S; Ramsey, J; Holt, DW; Wood, DM (2008). "Detection of the pharmaceutical agent glaucine as a recreational drug". European journal of clinical pharmacology 64 (5): 553–4. doi:10.1007/s00228-007-0451-9. PMID 18204834. 
  10. ^ Nestler E, Hyman S & Malenka R. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). China: McGraw-Hill Companies.
  11. ^ Asencio, M; Hurtado-Guzmán, C; López, JJ; Cassels, BK; Protais, P; Chagraoui, A (2005). "Structure-affinity relationships of halogenated predicentrine and glaucine derivatives at D1 and D2 dopaminergic receptors: Halogenation and D1 receptor selectivity". Bioorganic & Medicinal Chemistry 13 (11): 3699–704. doi:10.1016/j.bmc.2005.03.022. PMID 15862999. 
  12. ^ Orallo, F; Fernández Alzueta, A; Campos-Toimil, M; Calleja, JM (1995). "Study of the in vivo and in vitro cardiovascular effects of (+)-glaucine and N-carbethoxysecoglaucine in rats". British Journal of Pharmacology 114 (7): 1419–27. doi:10.1111/j.1476-5381.1995.tb13364.x. PMC 1510273. PMID 7606346. 
  13. ^ Zetler, G (1988). "Neuroleptic-like, anticonvulsant and antinociceptive effects of aporphine alkaloids: Bulbocapnine, corytuberine, boldine and glaucine". Archives internationales de pharmacodynamie et de therapie 296: 255–81. PMID 2907279.