Bulbocapnine Explained

Drug Name:	Bulbocapnine
Cas Number:	298-45-3
Pubchem:	12441
Chemspiderid:	11934
Unii:	O0TGI865QO
Kegg:	C09367
Chebi:	3211
Chembl:	157912
Synonyms:	Bulbokaprin
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
C:	19
H:	19
N:	1
O:	4
Smiles:	O1c4c(OC1)c3c2c(O)c(OC)ccc2C[C@H]5c3c(c4)CCN5C
Stdinchi:	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
Stdinchikey:	LODGIKWNLDQZBM-LBPRGKRZSA-N
Melting Point:	201 to 203
Melting Notes:	Racemate 213–214 °C

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).

Notes and References

1. CRC World Dictionary of Medicinal and Poisonous Plants: Common Names ... p.1142.
2. Adsersen A, Kjølbye A, Dall O, Jäger AK . Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Corydalis cava Schweigg. & Kort . Journal of Ethnopharmacology . 113 . 1 . 179–182 . August 2007 . 17574358 . 10.1016/j.jep.2007.05.006 .
3. Zhang YH, Shin JS, Lee SS, Kim SH, Lee MK . Inhibition of tyrosine hydroxylase by bulbocapnine . Planta Medica . 63 . 4 . 362–363 . August 1997 . 9270381 . 10.1055/s-2006-957702 . 29474171 .
4. Shin JS, Kim KT, Lee MK . Inhibitory effects of bulbocapnine on dopamine biosynthesis in PC12 cells . Neuroscience Letters . 244 . 3 . 161–164 . March 1998 . 9593514 . 10.1016/s0304-3940(98)00148-7 . 2415472 .
5. Lashuel HA, Hartley DM, Balakhaneh D, Aggarwal A, Teichberg S, Callaway DJ . 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 . November 2002 . 12167652 . 10.1074/jbc.M206593200 . free .
6. Web site: Dorlands Medical Dictionary at Merck . 2006-12-25 . https://web.archive.org/web/20080301182012/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_b_26zPzhtm . 2008-03-01 . dead .
7. Book: Scheflin AW, Opton EM . 1978 . The Mind Manipulators: A non-fiction Account . Paddington Press . New York . 0-448-22977-3 . 314–315 .
8. News: CIA Revelations: Behavior Control. https://web.archive.org/web/20170123120237/https://www.cia.gov/library/readingroom/docs/CIA-RDP99-00498R000100100019-3.pdf. dead. January 23, 2017. 24 January 2017. ABC News. Radio TV Reports. 20 July 1977.
9. Loizzo A, De Carolis AS, Longo VG . Studies on the central effects of bulbocapnine . Psychopharmacologia . 22 . 3 . 234–249 . September 1971 . 5316197 . 10.1007/BF00401786 . 41534659 .
10. Book: 10.1016/B978-0-407-00308-8.50018-5 . Stupor and akinetic mutism . Contemporary Neurology . 1984 . Johnson J . 96–102 . 978-0-407-00308-8 . https://books.google.com/books?id=yJujAgAAQBAJ&pg=PA96.
11. Book: de Jong HH . Experimental catatonia, a general reaction-form of the central nervous system and its implications for human pathology . 1945 . The Williams & Wilkins Company . 6 . 989851203 .