It was believed that only the (S)-form of glaucine occurs in nature until (R)-glaucine was found in fire poppy (Papaver californicum).[13]
Glaucine (2 stereoisomers)
(S)-configuration
(R)-configuration
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.[6] 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.[14] In this way, glaucine can prevent smooth muscle from contracting, allowing it to relax.
Glaucine has also recently[12] been found to have an effect on the neuronal 5-HT2A receptors, which are responsible for the hallucinogenic effects of classical
psychedelics. It also inhibits MAO enzymes.[16] Its enantiomers effect are same for adrenergic receptor yet different for 5-HT receptor. Both (R)-Glaucine and (S)-Glaucine antagonizes
α1 receptor but (S)-Glaucine is partial agonist of
5-HT2 subtypes whereas (R)-Glaucine is
positive allosteric modulator of 5-HT2.[17]
Uses
Medical
It is currently used as an
antitussive agent in
Iceland, as well as
Romania,
Bulgaria,
Russia and other eastern European countries.[6][11] 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.[6]
Glaucine has been reported to reduce blood pressure, heart rate and possess anticonvulsant and antinoiciceptive effect in animals[18][19]
Recreational
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.[10][11] 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".[10]
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".[11]
^Lapa GB, Sheichenko OP, Serezhechkin AG, Tolkachev ON (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.
ISSN0091-150X.
S2CID44040818. S-(+)-Glaucine (C21H25NO4) is the main alkaloid component in the grass of yellow horn poppy (Glaucium luteum L., syn. Glaucium flavum Crantz) of the family Papaveraceae
^Xu XH, Yu GD, Wang ZT (May 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.
PMID15706885.
^Morteza-Semnani K, Amin G, Shidfar MR, Hadizadeh H, Shafiee A (July 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.
PMID12837370.
^Milanowski DJ, Winter RE, Elvin-Lewis MP, Lewis WH (June 2002). "Geographic distribution of three alkaloid chemotypes of Croton lechleri". Journal of Natural Products. 65 (6): 814–9.
doi:
10.1021/np000270v.
PMID12088421.
^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.
PMID2907279.
^Rovinskiĭ VI (September 1989). "[A case of hallucinogen-like action of glaucine]". Klinicheskaia Meditsina. 67 (9): 107–8.
PMID2586025.
^
abcRovinskiĭ VI (2006). "[Acute glaucine syndrome in the physician's practice: the clinical picture and potential danger]". Klinicheskaia Meditsina. 84 (11): 68–70.
PMID17243616.
^
abcdeDargan PI, Button J, Hawkins L, Archer JR, Ovaska H, Lidder S, et al. (May 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.
PMID18204834.
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^
abHeng, HL, Chee, CF, Thy, CK, et al. In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5‐HT2 and α1 receptors. Chem Biol Drug Des. 2019; 93: 132– 138.
https://doi.org/10.1111/cbdd.13390
^Heng HL, Chee CF, Thy CK, Tee JT, Chin SP, Herr DR, Buckle MJ, Paterson IC, Doughty SW, Abd Rahman N, Chung LY (February 2019). "In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors". Chemical Biology & Drug Design. 93 (2): 132–138.
doi:
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PMID30216681.
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^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.
PMID2907279.