Bulbocapnine

Bulbocapnine
Clinical data
Other names	Bulbokaprin
Identifiers
	IUPAC name (12S)-17-methoxy-11-methyl-3,5-dioxa-11-azapentacyclo[10.7.1.02,6.08,20.014,19]icosa-1(20),2(6),7,14(19),15,17-hexaen-18-ol;
CAS Number	298-45-3;
PubChem CID	12441;
ChemSpider	11934;
UNII	O0TGI865QO;
KEGG	C09367;
ChEBI	CHEBI:3211;
ChEMBL	ChEMBL157912;
CompTox Dashboard (EPA)	DTXSID20183940 ;
ECHA InfoCard	100.005.511
Chemical and physical data
Formula	C19H19NO4
Molar mass	325.364 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	201 to 203 °C (394 to 397 °F) ; Racemate 213–214 °C
	SMILES O1c4c(OC1)c3c2c(O)c(OC)ccc2C[C@H]5c3c(c4)CCN5C;
	InChI InChI=1S/C19H19NO4/c1-20-6-5-11-8-14-19(24-9-23-14)17-15(11)12(20)7-10-3-4-13(22-2)18(21)16(10)17/h3-4,8,12,21H,5-7,9H2,1-2H3/t12-/m0/s1; Key:LODGIKWNLDQZBM-LBPRGKRZSA-N;

Bulbocapnine is an alkaloid found in Corydalis (notably the European species C. cava) and Dicentra, genera of the plant family Fumariaceae which have caused (notably the American species Corydalis caseana) the fatal poisoning of sheep and cattle.^[1] It has been shown to act as an acetylcholinesterase inhibitor,^[2] and inhibits biosynthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase.^[3]^[4] Like apomorphine, it is reported to be an inhibitor of amyloid beta protein (Aβ) fiber formation, whose presence is a hallmark of Alzheimer's disease (AD). Bulbocapnine is thus a potential therapeutic under the amyloid hypothesis.^[5] According to the Dorlands Medical Dictionary, it "inhibits the reflex and motor activities of striated muscle. It has been used in the treatment of muscular tremors and vestibular nystagmus".^[6]

A psychiatrist at Tulane University named Robert Heath carried out experiments on prisoners at the Louisiana State Penitentiary using bulbocapnine to induce stupor.^[7] This work at Tulane inspired, and was continued parallel to, experiments carried out at the behest of the Central Intelligence Agency. The bulbocapnine work Heath conducted for the government was one component of a large investigation into the potential of psychoactive compounds as aids to interrogation.^[8]

Effects

It can induce catalepsy featuring the curious symptom of waxy flexibility^[9] and the state produced by the drug has been compared to Akinetic mutism.^[10]^[11]

In popular culture

In literature

The author William S. Burroughs references the drug in his book Naked Lunch (1959), in which the fictional Dr. Benway uses it to induce obedience in torture victims.

In television

The drug's use to treat Mayor Kane's father-in-law and predecessor is a plot point in season 2 of the TV series Boss, e.g., in episodes s2.e8 ("Consequences"; October 5, 2012) and s2.e9 ("Church"; October 12, 2012).

References

^ CRC World Dictionary of Medicinal and Poisonous Plants: Common Names ... p.1142.
^ Adsersen A, Kjølbye A, Dall O, Jäger AK (August 2007). "Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Corydalis cava Schweigg. & Kort". Journal of Ethnopharmacology. 113 (1): 179–182. doi:10.1016/j.jep.2007.05.006. PMID 17574358.
^ Zhang YH, Shin JS, Lee SS, Kim SH, Lee MK (August 1997). "Inhibition of tyrosine hydroxylase by bulbocapnine". Planta Medica. 63 (4): 362–363. doi:10.1055/s-2006-957702. PMID 9270381. S2CID 29474171.
^ Shin JS, Kim KT, Lee MK (March 1998). "Inhibitory effects of bulbocapnine on dopamine biosynthesis in PC12 cells". Neuroscience Letters. 244 (3): 161–164. doi:10.1016/s0304-3940(98)00148-7. PMID 9593514. S2CID 2415472.
^ Lashuel HA, Hartley DM, Balakhaneh D, Aggarwal A, Teichberg S, Callaway DJ (November 2002). "New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's disease". The Journal of Biological Chemistry. 277 (45): 42881–42890. doi:10.1074/jbc.M206593200. PMID 12167652.
^ "Dorlands Medical Dictionary at Merck". Archived from the original on 2008-03-01. Retrieved 2006-12-25.
^ Scheflin AW, Opton EM (1978). The Mind Manipulators: A non-fiction Account. New York: Paddington Press. pp. 314–315. ISBN 0-448-22977-3.
^ "CIA Revelations: Behavior Control" (PDF). Radio TV Reports. ABC News. 20 July 1977. Archived from the original (PDF) on January 23, 2017. Retrieved 24 January 2017.
^ Loizzo A, De Carolis AS, Longo VG (September 1971). "Studies on the central effects of bulbocapnine". Psychopharmacologia. 22 (3): 234–249. doi:10.1007/BF00401786. PMID 5316197. S2CID 41534659.
^ Johnson J (1984). "Stupor and akinetic mutism". Contemporary Neurology. pp. 96–102. doi:10.1016/B978-0-407-00308-8.50018-5. ISBN 978-0-407-00308-8.
^ de Jong HH (1945). Experimental catatonia, a general reaction-form of the central nervous system and its implications for human pathology. The Williams & Wilkins Company. p. 6. OCLC 989851203.

[1] CRC World Dictionary of Medicinal and Poisonous Plants: Common Names ... p.1142.

[2] Adsersen A, Kjølbye A, Dall O, Jäger AK (August 2007). "Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Corydalis cava Schweigg. & Kort". Journal of Ethnopharmacology. 113 (1): 179–182. doi:10.1016/j.jep.2007.05.006. PMID 17574358.

[3] Zhang YH, Shin JS, Lee SS, Kim SH, Lee MK (August 1997). "Inhibition of tyrosine hydroxylase by bulbocapnine". Planta Medica. 63 (4): 362–363. doi:10.1055/s-2006-957702. PMID 9270381. S2CID 29474171.

[4] Shin JS, Kim KT, Lee MK (March 1998). "Inhibitory effects of bulbocapnine on dopamine biosynthesis in PC12 cells". Neuroscience Letters. 244 (3): 161–164. doi:10.1016/s0304-3940(98)00148-7. PMID 9593514. S2CID 2415472.

[lashuel-5] Lashuel HA, Hartley DM, Balakhaneh D, Aggarwal A, Teichberg S, Callaway DJ (November 2002). "New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's disease". The Journal of Biological Chemistry. 277 (45): 42881–42890. doi:10.1074/jbc.M206593200. PMID 12167652.

[6] "Dorlands Medical Dictionary at Merck". Archived from the original on 2008-03-01. Retrieved 2006-12-25.

[7] Scheflin AW, Opton EM (1978). The Mind Manipulators: A non-fiction Account. New York: Paddington Press. pp. 314–315. ISBN 0-448-22977-3.

[8] "CIA Revelations: Behavior Control" (PDF). Radio TV Reports. ABC News. 20 July 1977. Archived from the original (PDF) on January 23, 2017. Retrieved 24 January 2017.

[9] Loizzo A, De Carolis AS, Longo VG (September 1971). "Studies on the central effects of bulbocapnine". Psychopharmacologia. 22 (3): 234–249. doi:10.1007/BF00401786. PMID 5316197. S2CID 41534659.

[10] Johnson J (1984). "Stupor and akinetic mutism". Contemporary Neurology. pp. 96–102. doi:10.1016/B978-0-407-00308-8.50018-5. ISBN 978-0-407-00308-8.

[11] Jong HH (1945). Experimental catatonia, a general reaction-form of the central nervous system and its implications for human pathology. The Williams & Wilkins Company. p. 6. OCLC 989851203.

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