The Serpent and the Rainbow (1988): a Pathophysiological Model for Tetrodotoxin Overdose
Abstract The Serpent and the Rainbow (1988) is an attractive teaching model that combines pharmacology and physiological alterations in many functional systems. Based on a true event, this horror classic turned into a cult film analyzes how the scientific method is capable of providing answers to the myth of the living dead through voodoo, in the population of Haiti, due to the inhalation of a powerful powder drug that contains high doses of tetrodotoxin. This film simulates the acute state of catalepsy of the patients and the tests submitted to certify the apparent death after confirmation of the irreversible cessation of cardiorespiratory or brain functions, due to the absence of brainstem reflexes from the long-term effects of the drug. Furthermore, although the patient does not die and is buried while being aware of the entire process, the film allows the students to reflect on the high psychological burden, both of the patient himself and of the population, which deepens the states of terror by assuming who is a slave returned from death without soul and without will.
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Davis W. La Serpiente y el Arco Iris: Historia secreta de la magia, los zombis y el vudú. Buenos Aires, Argentina: Emece Editores; 1985.
Gorelik O, Feldman L, Cohen N. Heart failure and orthostatic hypotension. Heart Fail. Rev. 2016;21(5):529-538.
Memmer MK. Acute orthostatic hypotension. Heart Lung. 1988;17(2):134-143.
Rozenberg J, Wieling W, Schon IK, Westerhof B, Frampton C, Jardine D. MSNA during prolonged post-faint hypotension. Clin. Auton. Res. 2012;22(4):167-173. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412950/
De Ryck M, Teitelbaum P. Morphine catalepsy as an adaptive reflex state in rats. Behav. Neurosci. 1984;98(2):243-261.
Escalante-Cobo JL. Muerte encefálica. Evolución histórica y situación actual. Med. Intensiva. 2000;24:97-105. https://www.medintensiva.org/es-pdf-X0210569100903228
Guidelines for the determination of death. Report of the medical consultants on the diagnosis of death to the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. JAMA. 1981;246(19):2184-2186.
Hills TE. Determinación de la muerte cerebral Revisión de las directrices basadas en la evidencia. Nursing. 2011;29(3):16-22. https://www.elsevier.es/es-revista-nursing-20-pdf-S0212538211701984
Martínez-Martín P, Martínez Sarriés FJ. Actividad motora espontánea y refleja en la muerte cerebral [Spontaneous and reflex motor behavior in brain death]. Neurologia. 1994;9(9):407-409.
Escudero-Augusto D. Diagnóstico clínico de muerte encefálica. Prerrequisitos y exploración neurológica. Med. Intensiva. 2000;24:106-15. https://www.medintensiva.org/es-pdf-X0210569100903236
Paniagua-Soto J, Piñero-Benítez M. Muerte encefálica: ¿cuál es el valor diagnóstico de los potenciales evocados multimodales? Med. Intensiva. 2000;24:124-34. https://www.medintensiva.org/es-pdf-X021056910090321X
Craan AG. Toxicologic aspects of voodoo in Haiti. Biomed. Environ. Sci. 1988;1(4):372-381.
Davis EW. The ethnobiology of the Haitian zombi. J. Ethnopharmacol. 1983;9(1):85-104.
Chen R, Chung SH. Mechanism of tetrodotoxin block and resistance in sodium channels. Biochem. Biophys. Res. Commun. 2014;446(1):370-374. https://www.sciencedirect.com/science/article/pii/S0006291X14003945
Borison HL, McCarthyle, Clark WG, Radhakrishan N. Vomiting, hypothermia, and respiratory paralysis due to tetrodotoxin (puffer fish poison) in the cat. Toxicol. Appl. Pharmacol. 1963;5:350-357.
Ahasan HA, Mamun AA, Karim SR, Bakar MA, Gazi EA, Bala CS. Paralytic complications of puffer fish (tetrodotoxin) poisoning. Singapore Med. J. 2004;45(2):73-74. https://www.sma.org.sg/smj/4502/4502a2.pdf
Islam QT, Razzak MA, Islam MA, et al. Puffer fish poisoning in Bangladesh: clinical and toxicological results from large outbreaks in 2008. Trans. R. Soc. Trop. Med. Hyg. 2011;105(2):74-80.
Bucciarelli GM, Lechner M, Fontes A, Kats LB, Eisthen HL, Shaffer HB. From Poison to Promise: The Evolution of Tetrodotoxin and Its Potential as a Therapeutic. Toxins. 2021;13(8):517. https://doi.org/10.3390/toxins13080517
Liu SH, Tseng CY, Lin CC. Is neostigmine effective in severe pufferfish-associated tetrodotoxin poisoning? Clin. Toxicol. (Phila). 2015;53(1):13-21.
Magarlamov TY, Melnikova DI, Chernyshev AV. Tetrodotoxin-Producing Bacteria: Detection, Distribution and Migration of the Toxin in Aquatic Systems. Toxins. 2017;9(5):166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450714/pdf/toxins-09-00166.pdf
Benedek C, Rivier L. Evidence for the presence of tetrodotoxin in a powder used in Haiti for zombification. Toxicon. 1989;27(4):473-480.
Näkki R, Koistinaho J, Sharp FR, Sagar SM. Cerebellar toxicity of phencyclidine. J. Neurosci. 1995;15(3 Pt 2):2097-2108. https://doi.org/10.1523/JNEUROSCI.15-03-02097.1995
Aguayo LG, Albuquerque EX. Phencyclidine blocks two potassium currents in spinal neurons in cell culture. Brain Res. 1987;436(1):9-17.
Mount H, Boksa P, Chaudieu I, Quirion R. Phencyclidine and related compounds evoked [3H]dopamine release from rat mesencephalic cell cultures by a mechanism independent of the phencyclidine receptor, sigma binding site, or dopamine uptake site. Can. J. Physiol. Pharmacol. 1990;68(9):1200-1206.
Carrazana E, DeToledo J, Tatum W, Rivas-Vasquez R, Rey G, Wheeler S. Epilepsy and religious experiences: Voodoo possession. Epilepsia. 1999;40(2):239-241. https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1528-1157.1999.tb02081.x
Weil AT, Davis W. Bufo alvarius: a potent hallucinogen of animal origin. J. Ethnopharmacol. 1994;41(1-2):1-8.
McBride MC. Bufotenine: toward an understanding of possible psychoactive mechanisms. J. Psychoactive Drugs. 2000;32(3):321-331.
Emanuele E, Colombo R, Martinelli V, et al. Elevated urine levels of bufotenine in patients with autistic spectrum disorders and schizophrenia. Neuro Endocrinol. Lett. 2010;31(1):117-121.
Takeda N, Ikeda R, Ohba K, Kondo M. Bufotenine reconsidered as a diagnostic indicator of psychiatric disorders. Neuroreport. 1995;6(17):2378-2380.
Gorelik O, Feldman L, Cohen N. Heart failure and orthostatic hypotension. Heart Fail. Rev. 2016;21(5):529-538.
Memmer MK. Acute orthostatic hypotension. Heart Lung. 1988;17(2):134-143.
Rozenberg J, Wieling W, Schon IK, Westerhof B, Frampton C, Jardine D. MSNA during prolonged post-faint hypotension. Clin. Auton. Res. 2012;22(4):167-173. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412950/
De Ryck M, Teitelbaum P. Morphine catalepsy as an adaptive reflex state in rats. Behav. Neurosci. 1984;98(2):243-261.
Escalante-Cobo JL. Muerte encefálica. Evolución histórica y situación actual. Med. Intensiva. 2000;24:97-105. https://www.medintensiva.org/es-pdf-X0210569100903228
Guidelines for the determination of death. Report of the medical consultants on the diagnosis of death to the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. JAMA. 1981;246(19):2184-2186.
Hills TE. Determinación de la muerte cerebral Revisión de las directrices basadas en la evidencia. Nursing. 2011;29(3):16-22. https://www.elsevier.es/es-revista-nursing-20-pdf-S0212538211701984
Martínez-Martín P, Martínez Sarriés FJ. Actividad motora espontánea y refleja en la muerte cerebral [Spontaneous and reflex motor behavior in brain death]. Neurologia. 1994;9(9):407-409.
Escudero-Augusto D. Diagnóstico clínico de muerte encefálica. Prerrequisitos y exploración neurológica. Med. Intensiva. 2000;24:106-15. https://www.medintensiva.org/es-pdf-X0210569100903236
Paniagua-Soto J, Piñero-Benítez M. Muerte encefálica: ¿cuál es el valor diagnóstico de los potenciales evocados multimodales? Med. Intensiva. 2000;24:124-34. https://www.medintensiva.org/es-pdf-X021056910090321X
Craan AG. Toxicologic aspects of voodoo in Haiti. Biomed. Environ. Sci. 1988;1(4):372-381.
Davis EW. The ethnobiology of the Haitian zombi. J. Ethnopharmacol. 1983;9(1):85-104.
Chen R, Chung SH. Mechanism of tetrodotoxin block and resistance in sodium channels. Biochem. Biophys. Res. Commun. 2014;446(1):370-374. https://www.sciencedirect.com/science/article/pii/S0006291X14003945
Borison HL, McCarthyle, Clark WG, Radhakrishan N. Vomiting, hypothermia, and respiratory paralysis due to tetrodotoxin (puffer fish poison) in the cat. Toxicol. Appl. Pharmacol. 1963;5:350-357.
Ahasan HA, Mamun AA, Karim SR, Bakar MA, Gazi EA, Bala CS. Paralytic complications of puffer fish (tetrodotoxin) poisoning. Singapore Med. J. 2004;45(2):73-74. https://www.sma.org.sg/smj/4502/4502a2.pdf
Islam QT, Razzak MA, Islam MA, et al. Puffer fish poisoning in Bangladesh: clinical and toxicological results from large outbreaks in 2008. Trans. R. Soc. Trop. Med. Hyg. 2011;105(2):74-80.
Bucciarelli GM, Lechner M, Fontes A, Kats LB, Eisthen HL, Shaffer HB. From Poison to Promise: The Evolution of Tetrodotoxin and Its Potential as a Therapeutic. Toxins. 2021;13(8):517. https://doi.org/10.3390/toxins13080517
Liu SH, Tseng CY, Lin CC. Is neostigmine effective in severe pufferfish-associated tetrodotoxin poisoning? Clin. Toxicol. (Phila). 2015;53(1):13-21.
Magarlamov TY, Melnikova DI, Chernyshev AV. Tetrodotoxin-Producing Bacteria: Detection, Distribution and Migration of the Toxin in Aquatic Systems. Toxins. 2017;9(5):166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450714/pdf/toxins-09-00166.pdf
Benedek C, Rivier L. Evidence for the presence of tetrodotoxin in a powder used in Haiti for zombification. Toxicon. 1989;27(4):473-480.
Näkki R, Koistinaho J, Sharp FR, Sagar SM. Cerebellar toxicity of phencyclidine. J. Neurosci. 1995;15(3 Pt 2):2097-2108. https://doi.org/10.1523/JNEUROSCI.15-03-02097.1995
Aguayo LG, Albuquerque EX. Phencyclidine blocks two potassium currents in spinal neurons in cell culture. Brain Res. 1987;436(1):9-17.
Mount H, Boksa P, Chaudieu I, Quirion R. Phencyclidine and related compounds evoked [3H]dopamine release from rat mesencephalic cell cultures by a mechanism independent of the phencyclidine receptor, sigma binding site, or dopamine uptake site. Can. J. Physiol. Pharmacol. 1990;68(9):1200-1206.
Carrazana E, DeToledo J, Tatum W, Rivas-Vasquez R, Rey G, Wheeler S. Epilepsy and religious experiences: Voodoo possession. Epilepsia. 1999;40(2):239-241. https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1528-1157.1999.tb02081.x
Weil AT, Davis W. Bufo alvarius: a potent hallucinogen of animal origin. J. Ethnopharmacol. 1994;41(1-2):1-8.
McBride MC. Bufotenine: toward an understanding of possible psychoactive mechanisms. J. Psychoactive Drugs. 2000;32(3):321-331.
Emanuele E, Colombo R, Martinelli V, et al. Elevated urine levels of bufotenine in patients with autistic spectrum disorders and schizophrenia. Neuro Endocrinol. Lett. 2010;31(1):117-121.
Takeda N, Ikeda R, Ohba K, Kondo M. Bufotenine reconsidered as a diagnostic indicator of psychiatric disorders. Neuroreport. 1995;6(17):2378-2380.
Fernández-Martos, C., Suleiman-Martos, N., Gómez-Urquiza, J. L., Prieto-Gómez, I., Ramírez-Sánchez, M., Segarra-Robles, A. B., García-Cózar, F., & Domínguez-Vías, G. (2024). The Serpent and the Rainbow (1988): a Pathophysiological Model for Tetrodotoxin Overdose. Journal of Medicine and Movies, 20(3), 285–300. https://doi.org/10.14201/rmc.32031
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