Glaucine
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| 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 |
| Pregnancy cat. | ? |
| Legal status | ? |
| Identifiers | |
| CAS number | 475-81-0  5630-11-5 |
| ATC code | None |
| PubChem | CID 16754 |
| ChemSpider | 15883  |
| UNII | NU19306XA7 |
| KEGG | D08014 |
| ChEMBL | CHEMBL228082 |
| NIAID ChemDB | 011385 |
| Chemical data | |
| Formula | C21H25NO4 |
| Mol. mass | 355.428 g/mol |
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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]
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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.[10] 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.[11] 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.[12][13] 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.[14]
Clinical Use [edit]
It is currently used as an antitussive agent in Romania, Bulgaria, Iceland, Russia and other eastern European countries.[15][16] 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.[17]
Animal studies demonstrate the ability of glaucine to decrease heart rate and lower blood pressure,[18] 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.[19] 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.[20][21] 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”.[22]
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”.[23]
See also [edit]
References [edit]
- ^ 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"
- ^ Xu XH, Yu GD, Wang ZT. Resource investigation and quality evaluation on wild Corydalis yanhusuo. (Chinese). Zhongguo Zhong Yao Za Zhi. 2004 May;29(5):399-401. PMID 15706885
- ^ Morteza-Semnani K, Amin G, Shidfar MR, Hadizadeh H, Shafiee A. Antifungal activity of the methanolic extract and alkaloids of Glaucium oxylobum. Fitoterapia. 2003 Jul;74(5):493-6. PMID 12837370
- ^ Milanowski DJ, Winter RE, Elvin-Lewis MP, Lewis WH. Geographic distribution of three alkaloid chemotypes of Croton lechleri. Journal of Natural Products. 2002 Jun;65(6):814-9. PMID 12088421
- ^ Cortijo J, Villagrasa V, Pons R, Berto L, Martí-Cabrera M, Martinez-Losa M, Domenech T, Beleta J, Morcillo EJ. Bronchodilator and anti-inflammatory activities of glaucine: In vitro studies in human airway smooth muscle and polymorphonuclear leukocytes. British Journal of Pharmacology. 1999 Aug;127(7):1641-51. PMID 10455321
- ^ Rühle KH, Criscuolo D, Dieterich HA, Köhler D, Riedel G. Objective evaluation of dextromethorphan and glaucine as antitussive agents. British Journal of Clinical Pharmacology. 1984 May;17(5):521-4. PMID 6375709
- ^ Rovinskiĭ VI. A case of hallucinogen-like action of glaucine. (Russian). Klinicheskaia Meditsina (Mosk). 1989 Sep;67(9):107-8. PMID 2586025
- ^ Rovinskiĭ VI. Acute glaucine syndrome in the physician's practice: the clinical picture and potential danger. (Russian). Klinicheskaia Meditsina (Mosk). 2006;84(11):68-70. PMID 17243616
- ^ Dargan PI, Button J, Hawkins L, Archer JR, Ovaska H, Lidder S, Ramsey J, Holt DW, Wood DM. Detection of the pharmaceutical agent glaucine as a recreational drug. European Journal of Clinical Pharmacology. 2008 May;64(5):553-4. PMID 18204834
- ^ Cortijo J et al (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. PMID 10455321
- ^ Nestler E, Hyman S & Malenka R. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). China: McGraw-Hill Companies.
- ^ Asencio M, et al (2005). Structure-affinity relationships of halogenated predicentrine and glaucine derivatives at D1 and D2 dopaminergic receptors: Halogenation and D1 receptor selectivity. Biorganic & Medicinal Chemistry 13:3699-3704. PMID 15862999
- ^ Dargan PI et al (2008). Detection of the pharmaceutical agent glaucine as a recreational drug. European Journal of Clinical Pharmacology 64:553-554. PMID 18204834
- ^ Cortijo J et al (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. PMID 10455321
- ^ Cortijo J et al (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. PMID 10455321
- ^ Dargan PI et al (2008). Detection of the pharmaceutical agent glaucine as a recreational drug. European Journal of Clinical Pharmacology 64:553-554. PMID 18204834
- ^ Cortijo J et al (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. PMID 10455321
- ^ Orallo F, et al (1995). Study of the in vivo and in vitro cardiovascular effects of (+)-glaucine and N-carbethoxysecoglaucine in rats. British Journal of Pharmacology 114:1419-1427. PMID 7606346
- ^ Zetler G (1988). Neuroleptic-like, anticonvulsant and antinociceptive effects of aporphine alkaloids: bulbocapnine, corytuberine, boldine and glaucine. Archives internationales de pharmacodynamie et de therapie 296:255-281. PMID 2907279
- ^ Dargan PI et al (2008). Detection of the pharmaceutical agent glaucine as a recreational drug. European Journal of Clinical Pharmacology 64:553-554. PMID 18204834
- ^ Rovinskiĭ VI (2006). [Acute glaucine syndrome in the physician's practice: the clinical picture and potential danger]. Klin Med (Mosk) 84(11):68-70. PMID 17243616
- ^ Rovinskiĭ VI (2006). [Acute glaucine syndrome in the physician's practice: the clinical picture and potential danger]. Klin Med (Mosk) 84(11):68-70. PMID 17243616
- ^ Dargan PI et al (2008). Detection of the pharmaceutical agent glaucine as a recreational drug. European Journal of Clinical Pharmacology 64:553-554. PMID 18204834
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