Glaucine

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Glaucine
File: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 7pxY
5630-11-5
ATC code None
PubChem CID 16754
ChemSpider 15883 7pxN
UNII NU19306XA7 7pxN
KEGG D08014 7pxN
ChEMBL CHEMBL228082 7pxN
NIAID ChemDB 011385
Chemical data
Formula C21H25NO4 
Mol. mass 355.428 g/mol
 14pxN (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 recently been detected as a novel recreational drug.[9]

Mechanism of action

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

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

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

References

  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. ISSN 0091-150X. doi:10.1023/B:PHAC.0000048907.58847.c6. 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. PMID 12837370. doi:10.1016/s0367-326x(03)00113-8. 
  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. PMID 12088421. doi:10.1021/np000270v. 
  5. 5.0 5.1 5.2 5.3 5.4 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. PMC 1566148. PMID 10455321. doi:10.1038/sj.bjp.0702702. 
  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. PMC 1463443. PMID 6375709. doi:10.1111/j.1365-2125.1984.tb02384.x. 
  7. Rovinskiĭ, VI (1989). "A case of hallucinogen-like action of glaucine". Klinicheskaia meditsina 67 (9): 107–8. PMID 2586025. 
  8. 8.0 8.1 8.2 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. 9.0 9.1 9.2 9.3 9.4 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. PMID 18204834. doi:10.1007/s00228-007-0451-9. 
  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. PMID 15862999. doi:10.1016/j.bmc.2005.03.022. 
  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. PMC 1510273. PMID 7606346. doi:10.1111/j.1476-5381.1995.tb13364.x. 
  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. 
      
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