Publicado

2008-04-01

Biosynthesis of morphine: Its importance in Parkinson´s disease

Biosíntesis de la morfina: su importancia en la enfermedad de Parkinson

Palabras clave:

Parkinson disease, early diagnosis, biosynthesis, morphine. (en)
enfermedad de Parkinson, diagnóstico precoz, biosíntesis, morfina. (es)

Descargas

Autores/as

  • José Perea Sasiaín Doctor en Medicina y Cirugía; Universidad Nacional de Colombia, Facultad de Medicina.
We sketch present knowledge on the morphine biosynthetic pathway in Papaver somniferum L and in animals. Two main neurophysiological functions of morphine in man are discussed. To explain idiopathic Parkinson´s disease we hypothetically propose the damage of substantia nigra neurons by endogenous neurotoxins resulting from abnormal secondary metabolites of dopamine or similar substances. Metabolic tests should be designed to establish the faulty stages of morphine biosynthesis in parkinsonians. The levels of central nervous system (CNS) produced morphine should be estimated in blood plasma, targeting parkinsonian prone populations (depressed persons), and correlated with abnormal alleles. Early preclinical diagnosed patients should be managed first physiologically and nutritionally.
Se presenta una panorámica tabulada y gráfica de los conocimientos actuales sobre la biosíntesis de la morfina tanto en Papaver somniferum como en los animales. Hacemos un análisis general de dos funciones principales de la morfina en el ser humano y de la importancia de aclarar su biosíntesis para establecer las etapas defectuosas en los enfermos parkinsonianos. Se admite que el daño de las neuronas melánicas de la sustancia negra se produce por neurotoxinas endógenas, metabolitos anormales por cantidad o calidad, resultantes del metabolismo secundario de la dopamina lo cual desencadena la enfermedad de Parkinson idiopática. Deben diseñarse pruebas funcionales que permitan identificar dichos metabolitos en las poblaciones de alto riesgo genético y correlacionarlos con los alelos presentes en ellas. Se concluye que para un diagnóstico preclínico de la enfermedad de Parkinson idiopático es necesario comparar los niveles de morfina proveniente del sistema nervioso central en la sangre de personas normales y en parkinsonianos antes de cualquier tratamiento. Se recomienda un manejo fisiológico y dietético de estas personas (pre-parkinsonianos) antes de la aparición de los signos de la enfermedad.

Referencias

Huxtable RJ, Schwarz SK. The isolation of morphine-first principles in science and ethics. Mol Interv. 2001;1:189-91.

Preininger V. Chemotaxonomy of papaveraceae and fumariaceae. The Alkaloids. 29. Brossi A, ed. Orlando: Academic Press. 1986:1-98.

Hazum E, Sabatka JJ, Chang KJ, Findlay JWA, Cuatrecasas P. Morphine in cow and human milk: could dietary morphine constitute a ligand for specific morphine (µ) receptors? Science. 1981;213:1010-2.

Poeaknapo C. Mammalian morphine: de novo formation of morphine in human cells. Med Sci Monit. 2005;11:MS6-17.

Holmes HL. The morphine alkaloids, I. In The Alkaloids, vol II. Manske RHF, Holmes HL, eds. New York:

Academic Press. 1952: 2-159.

Holmes HL, Stork G. The morphine alkaloids, II. In The Alkaloids, vol II. Manske RHF, Holmes HL, eds. New York: Academic Press. 1952: 162-217.

Battersby AR, Foulkes DM, Binks R. Alkaloid biosynthesis. Part VIII. Use of optically active precursor for investigations on the biosynthesis of morphine alkaloids. J Chem Soc. 1965:3323-32.

Barton DHR, Kirby GW, Steglich W, Thomas GM, Battersby AR, Dobson TA, et al. Investigations on the biosynthesis of morphine alkaloids. J Chem Soc. 1965;2423-38.

Bruneton J. Farmacognosia, 2a. Edición. Villar del Fresno A, Carretero Acame E, Rebuelta Lizabe M. trads. Zaragoza: Acribia. 2001:917.

Boettcher C, Fellermeier M, Boettcher C, Dräger B, Zenk MH. How human neuroblastoma cells make morphine. Proc Nal Acad Sci USA. 2005;102:8495-500.

Kream RM, Stefano GB. De novo biosynthesis of morphine in animal cells-based model. Med Sci Monit. 2006;12:RA207-19.

Samanani N, Facchini PJ. Purification and characterization of norcoclaurine synthase.The first committed enzyme in benzylisoquinoline alkaloid biosynthesis in plants. J Biol Chem. 2002;277:33878-83.

Gopinath KW, Govindachari TR, Pai BR, Viswanathan N. The structure of reticuline, a new alkaloid from Annona reticulata. Chem Ber. 1959; 92: 776-9.

Brochmann-Hanssen E, Furuya T. New opium alkaloid. J Pharm Sci. 1964;53:575.

Sandler M, Johnson RD, Ruthven CRJ, Reid JL, Calne DB. Transamination is a major pathway of L-DOPA metabolism following peripheral decarboxylase inhibition. Nature. 1974;247:364-6.

Brossi A. Mammalian alkaloids: conversions of tetrahydroisoquinoline-1-carboxylic acids derived from dopamine. Planta Med. 1991;57(Sup 1) S93-100.

Coscia CJ, Burke W, Jamroz G, Lasala JM, McFarlane J, Mitchell J, et al. Ocurrence of a new class of tetrahydroisoquinoline alkaloids in L-dopa-treated parkinsonian patients. Nature. 1977;269:617-9.

Sandler M, Carter SB, Hunter KR, Stern GM. Tetrahydroisoquinoline alkaloids: in vivo metabolites of L-dopa in man. Nature. 1973;241:439-43.

Sango K, Maruyama W, Matsubara K, Dostert P, Minami C, Kawai M, et al. Enantio-selective occurrence of (S)-tetrahydropapaveroline in human brain. Neurosci Lett. 2000;283:224-6.

Meyerson LR, Cashaw JL, McMurtrey KD, Davis VE. Stereoselective enzymatic o-methylation of tetrahydropapaveroline and tetrahydroxyberbine alkaloids. Biochem Pharmacol. 1979;28:1745-52.

Cashaw JL, Ruchirawat S, Nimit Y, Davis VE. Regioselective o-methylation of tetrahydropapaveroline and tetrahydroberbine in vivo in rat brain. Biochem Pharmacol. 1983;32:3163-9.

Zhu W, Ma Y, Cadet P, Yu D, Bilfinger TV, Bianchi E, Stefano GB. Presence of reticuline in rat brain: a pathway for morphine biosynthesis. Brain Res Mol Brain Res. 2003;117:83-90.

Hirata K, Poeaknapo C, Schmidt J, Zenk MH. 1,2-dehydroreticuline synthase, the branch point enzyme opening the morphinan biosynthetic pathway. Phytochem. 2004;65:1039-46.

Borkowski AR, Horn JS, Rapoport H. Role of 1,2-dehydroreticulium ion in the biosynthetic conversion of reticuline to thebaine. J Am Chem Soc. 1978;100:276-81.

De-Eknambul W, Zenk MH. Purification and properties of 1,2-dehydroreticuline reductase from Papaver som-niferum seedlings. Phytochem. 1992;31:813-21.

Amann T, Roos PH, Huh H, Zenk MH. Purification and characterization of a cytochrome P 450 enzyme from pig liver, catalyzing the phenol oxidase coupling of R-reticuline to salutaridine, the critical step in morphine biogenesis. Heterocycles. 1995;40:425-40.

Weitz CJ, Faull KF, Goldstein A. Synthesis of the skeleton of the morphine molecule by mammalian liver. Nature. 1987;330:674-6.

Gerardy R, Zenk MH. Purification and characterization of salutaridine:NADPH 7-oxidoreductase from Papaver somniferum. Phytochem. 1993;34:125-32.

Grothe T, Lenz R, Kutchan TM. Molecular characterization of the salutaridinol 7-o-acetyltransferase involved in morphine biosynthesis in opium poppy Papaver somniferum. J Biol Chem. 2001;276:30717-23.

Lenz R, Zenk MH. Acetyl coenzyme A:salutaridinol-7-O-acetyltransferase from Papaver somniferum plant cell cultures. The enzyme catalyzing the formation of thebaine in morphine synthesis. J Biol Chem. 1995;270:31091-6.

Kodaira H, Lisek CA, Jardine I, Arimura A, Spector S. Identification of the convulsant opiate thebaine in mammalian brain. Proc Natl Acad Sci USA. 1989; 86:716-9.

Lenz R, Zenk MH. Purification and properties of codeinone reductase (NADPH) from Papaver somniferum cell cultures and differentiated plants.Eur J Biochem. 1995;233:132-9.

Unterlinner B, Lenz R, Kutchan TM. Molecular cloning and functional expression of codeinone reductase: the penultimate enzyme in morphine biosynthesis in the opium poppy Papaver somniferum. Planta J. 1999;18:565-75.

Kodaira H, Spector S. Transformation of thebaine to oripavine, codeine and morphine by rat liver, kidney and brain microsomes. Proc Natl Acad Sci USA. 1988;85:1267-71.

Mannering GJ, Dixon AC, Baker EM, Asami T. The in vivo liberation of morphine from codeine in man. J Pharmacol Exptl Ther. 1954;111:142-6.

Axelrod J. Enzymic conversion of codeine to morphine. J Pharmacol Exptl Ther. 1955;115:259-67.

Elison C, Elliott HW. Studies on the enzymatic N- and O-demethylation of narcotic analgesic and evidence for the formation of codeine from morphine in rats and dogs. J Pharmacol Exp Ther. 1964;144:265-75.

Nielsen B, Röe J, Brochmann-Hanssen E. Oripavine-a new opium alkaloid. Planta Med. 1983;48:205-6.

Brochmann-Hanssen E. A second pathway for the terminal steps in the biosynthesis of morphine. Planta Med. 1984;50:343-5.

Mikus G, Somogyi AA, Bochner F, Eichelbaum M. Thebaine O-demethylation to oripavine: genetic differences between two rat strains. Xenobiotica. 1991;21:1501-9.

Yamazoe Y, Numata H, Yamagita T. Thebaine metabolites in the urine of rhesus monkeys. Jpn J Pharmacol. 1981;31:433-42.

Kumagai Y, Todaka T, Toki S. A new metabolic pathway of morphine: in-vitro and in-vivo formation of morphinone and morphine-glutathione adduct in guinea pig. J Pharmacol Exp Ther. 1990;255:504-10.

Ishida T, Yano M, Toki S. In vivo formation of codeinone and morphinone from codeine. Isolation and identification from guinea pig bile. Drug Metabol Dispos. 1991;19:895-9.

Toki S, Yamano S. Production of morphinone as a metabolite of morphine and its physiological role. Yakugaku Zasshi. 1999;119:249-67.

Todaka T, Ishida T, Kita H, Narimatsu S, Yamano S. Bioactivation of morphine in human liver: isolation and identification of morphinone, a toxic metabolite. Biol Pharm Bull. 2005;28:1275-80.

Gates M, Tschudi G. The synthesis of morphine. J Am Chem Soc. 1956;78:1380-93.

Elad D, Ginsburg D. Synthesis in the morphine series. Part VI. The synthesis of morphine. J Chem Soc. 1954:3052-6.

Beyerman HC, Lie TS, Maat L, Bosman HH, Buurman E, Bijsterveld EJ, et al. A convenient synthesis of codeine and morphine. Rec Trav Chim Pays-Bas. 1976;95:24-5.

Mavrojannis M. L´action cataleptique de la morphine chez les rats. Contribution à la théorie toxique de la catalepsie. C R Soc Biol.1903;55:1092-4.

Davis VE, Walsh MJ. Alcohol, amines, and alkaloids: a possible biochemical basis for alcohol addiction. Science. 1970;167:1005-7.

Davis VE, Walsh MJ. Answer to Seevers letter. Science. 1970;170:1114-5.

Davis VE, Walsh MJ, Yamanaka Y. Augmentation of alkaloid formation from dopamine by alcohol and acetaldehyde in vitro. J Pharmacol Exptl Ther. 1970;174:401-412.

Seevers MH. Morphine and ethanol physical dependence: a critique of a hypothesis. Science. 1970;170:1113-4.

Sourkes TL. Possible new metabolites mediating the actions of L-Dopa. Nature. 1971;229:413-4.

Benyhe S. Minireview. Morphine: new aspects in the study of an ancient compound. Life Sci. 1994;55:969-79.

Meijerink WJ, Molina PE, Abumrad NN. Mammalian opiate alkaloid synthesis: lessons derived from plant biochemistry. Shock. 1999;12:165-73.

Hosztafi S, Fürst Z. Endogenous morphine. Pharmacol Res. 1995;32:15-20.

Poeaknapo C, Schmidt J, Brandsch M, Dräger B, Zenk MH. Endogenous formation of morphine in human cells. Proc Natl Acad Sci USA. 2004;101:14091-6.

Gintzler AR, Levy A, Spector S. Antibodies as a means of isolating and characterizing biologically active substances: Presence of a non-peptide, morphine-like compound in the central nervous system. Proc Natl Acad Sci USA. 1976;73:2132-6.

Donnerer J, Oka K, Brossi A, Rice KC, Spector S. Presence and formation of codeine and morphine in the rat. Proc Natl Acad Sci USA. 1986;83:4566-7.

Guarna M, Neri C, Petrioli F, Bianchi E. Potassium-induced release of endogenous morphine from rat brain slices. J Neurochem. 1998;70:147-52.

Molina PE, Hashiguchi Y, Meijerinck WJ, Naukam RJ, Boxer R, Abumrad NN. Modulation of endogenous opiate production: effect of fasting. Biochem Biophys Res Commun. 1995;207:312-7.

Goumon Y, Bouret S, Casares F, Zhu W, Beauvillain JC, Stefano GB. Lipopolysaccharide increases endogenous morphine levels in rat brain. Neurosci Lett. 2000;293:135-8.

Donnerer J, Cardinale G, Coffey J, Lisek CA, Jardine I, Spector S. Chemical characterization and regulation of endogenous morphine and codeine in rat. J Pharmacol Exptl Ther. 1987;242:583-7.

Lee CS, Spector S. Changes of endogenous morphine and codeine contents in the fasting rat. J Pharmacol Exp Ther. 1991;257:647-50.

Zhu W, Ma Y, Bell A, Esch T, Guarna M, Bilfinger TV, et al. Presence of morphine in rat amygdala: evidence for the mu3 opiate receptor subtype via nitric oxide release in limbic structures. Med Sci Monit. 2004;10:BR433-9.

Munjal ID, Minna JD, Manneckjee R, Bieck P, Spector S. Possible role of endogenous morphine and codeine on growth regulation of lung tissue. Life Sci. 1995;57:517-21.

Oka K, Kantrowitz JD, Spector S. Isolation of morphine from toad skin. Proc Natl Acad Sci USA. 1985;82:1852-4.

Haber H, Roske I, Rottmann M, Georgi M, Melzig MF. Alcohol induces formation of morphine precursors in the striatum of rats. Life Sci. 1997;60:79-89.

Gintzler AR, Gershon MD, Spector S. A non-peptide morphine-like compound: immunocytochemical localization in the mouse brain. Science. 1978:199:447-8.

Guarna M, Bianchi E, Bartolini A, Ghelardini C, Galeotti N, Bracci L, et al. Endogenous morphine modulates acute thermonociception in mice. J Neurochem. 2002;80:271-7.

Horak P, Haberman F, Spector S. Endogenous morphine and codeine in mice—effect of muramyl peptide. Life Sci. 1993;52:PL255-63.

Blume AJ, Shorr J, Finberg JPM, Spector S. Binding of the endogenous nonpeptide morphine-like compound to opiate receptors. Proc Natl Acad Sci USA. 1977;74:4927-31.

Epple A, Navarro I, Horak P, Spector S. Endogenous morphine and codeine: release by the chromaffin cells of the eel. Life Sci Pharmacol Let. 1993;52:117-21.

Kodaira H, Lisek CA, Jardine I, Arimura A, Spector S. Identification of the convulsant opiate thebaine in mammalian brain. Proc Natl Acad Sci USA. 1989;86:716-9.

Goldstein A, Barrett RW, James IF, Lowney LI, Weitz CJ, Knipmeyer LL, et al. Morphine and other opiates from beef brain and adrenal. Proc Natl Acad Sci USA. 1985;82:5203-7.

Killian AK, Schuster CR, House JT, Sholl S, Connors M, Wainer BH. A non-peptide morphine-like compound from brain. Life Sci. 1981;28:811-7.

Neri G, Guarna M, Bianchi E, Sonetti D, Matteucci G, Stefano GB. Endogenous morphine and codeine in the brain of non human primate. Med Sci Monit. 2004;10:MS1-5.

Liu Y, Bilfinger TV, Stefano GB. A rapid and sensitive quantitation method of endogenous morphine in human plasma. Life Sci. 1997;60:237-43.

Cardinale GJ, Donnerer J, Finck AD, Kantrowitz JD, Oka K, Spector S. Morphine and codeine are endogenous components of human cerebrospinal fluid. Life Sci. 1987;40:301-6.

Shorr J, Foley K, Spector S. Presence of a non-peptide morphine-like compound in human cerebrospinal fluid. Life Sci. 1978;23:2057-62.

Zhu W, Bilfinger TV, Baggerman G, Goumon Y, Stefano GB. Presence of endogenous morphine and morphine-6-glucuronide in human heart tissue. Int J Mol Med. 2001;7:419-22.

Zhu W, Cadet P, Baggerman G, Mantione KJ, Stefano GB. Human white blood cells synthesize morphine: CYP2D6 modulation. J Immunol. 2005;175:7357-62.

Boettcher C, Fischer W, Zenk MH. Comment on Human white blood cells synthesize morphine: CYP2D6 modulation. J Immunol. 2006;176:5703-4.

Brix-Christensen V, Tonnesen E, Sanchez RG, Bilfinger TV, Stefano GB. Endogenous morphine levels increase following cardiac surgery as part of the antiinflammatory response? Int J Cardiol. 1997;62:191-7.

Yoshida S, Ohta J, Yamasaki K, Kamei H, Harada Y, Yahara T, et al. Effect of surgical stress on endogenous morphine and cytokine levels in the plasma after laparoscopoic or open cholecystectomy. Surg Endosc. 2000;14:137-40.

Cadet P, Zhu W, Mantione KJ, Rymer M, Dardik I, Reisman S, et al. Cyclic exercise induces anti-inflammatory signal molecule increases in the plasma of Parkinson´s patients. Int J Mol Med. 2003;12:485-92.

Olsen P, Rasmussen M, Zhu W, Toennesen E, Stefano GB. Human gliomas contain morphine. Med Sci Monit. 2005;11:MS18-21.

Matsubara K, Fukushima S, Akane H, Kobayashi S, Shiono H. Increase urinary morphine, codeine and tetrahydropapaveroline in parkinsonian patient undergoing L-3,4-dihydroxyphenylalanine therapy: a possible biosynthetic pathway of morphine from L-3,4-dihydroxyphenylalanine in humans.J Pharmacol Exp Ther. 1992;260:974-8.

Mikus G, Bochner F, Eichelbaum M, Horak P, Somogyi AA, Spector S. Endogenous codeine and morphine in poor and extensive metabolisers of the CYP2D6 (debrisoquine/sparteine) polymorphism. J Pharmacol Exp Ther. 1994;268:546-51.

Hofmann U, Seefried S, Schweizer E, Ebner T, Mikus G, Eichelbaum M. Highly sensitive gas chromatographic-tandem mass spectrometric method for the determination of morphine and codeine in serum and urine in the femtomolar range. J Chromatogr B Biomed Sci Appl. 1999;727:81-8.

Stefano GB, Digenis A, Spector S, Leung MK, Bilfinger TV, Makman MH, et al. Opiate-like substances in an invertebrate, an opiate receptor on invertebrate and human immunocytes, and a role in immunosuppression.Proc Natl Acad Sci USA. 1993;90:11099-103.

Zhu W, Baggerman G, Goumon Y, Casares F, Brownawell B, Stefano GB. Presence of morphine and morphine-6-glucuronide in the marine mollusk Mytilus edulis ganglia determined by GC/MS and Q-TOF-MS. Starvation increases opiate alkaloid levels. Brain Res Mol Brain Res. 2001;88:155-60.

Sonetti D, Mola L, Casares F, Bianchi E, Guarna M, Stefano GB. Endogenous morphine levels increase in molluscan neural and immune tissues after physical trauma. Brain Res. 1999;835:137-47.

Goumon Y, Casares F, Zhu W, Stefano GB. The presence of morphine in ganglionic tissues of Modiolus deminissus: a highly sensitive method of quantitation for morphine and its derivatives. Brain Res Mol Brain Res. 2001;86:184-8.

Sonetti D, Peruzzi E, Stefano GB. Endogenous morphine and ACTH association in neural tissues. Med Sci Monit. 2005;11:MS22-30.

Casares FM, McElroy A, Mantione K, Baggermann G, Zhu W, Stefano GB. The american lobster, Homarus americanus, contains morphine that is coupled to nitric oxide release in its nervous and immune tissues: evidence for neurotransmitter and hormonal signaling. Neuro Endocrinol Lett. 2005;26:89-97.

Pryor SC, Elizee R. Evidence of opiates and opioid neuropeptides and their immune effects in parasitic invertebrates representing three different phyla: Schistosoma mansoni, Theromyzon tessulatum, Trichinella spiralis. Acta Biol Hung. 2000;51:331-41.

Leung MK, Dissous C, Capron A, Woldegaber H, Duvaux-Miret O, Pryor S, et al. Schistosoma mansoni: The presence and potential use of opiate-like substances. Exper Parasitol. 1995;81:208-15.

Zhu W, Baggerman G, Secor WE, Casares F, Pryor SC, Fricchione GL, et al. Dracunculus medinensis and Schistosoma mansoni contain opioid alkaloids. Ann Trop Med Parasit. 2002;96:309-16.

Goumon Y, Casares F, Pryor S, Ferguson L, Brownawell B, Cadet P, et al. Ascaris suum, an intestinal parasite, produces morphine. J Immunol. 2000;165:339-43.

Pryor SC, Henry S, Sarfo J. Endogenous morphine and parasitic helminthes. Med Sci Monit. 2005;11:RA183-9.

Kavaliers M, Podesta RB, Hirst M, Young B. Evidence for the activation of the endogenous opiate system in hamsters infected with human blood flukes, Schistosoma mansoni. Life Sci. 1984;35:2365-73.

Colwell DD, Kavaliers M. Evidence for involvement of endogenous opioid peptides in altered nociceptive responses of mice infected with Eimeria vermiformis. J Parasitol. 1993;79:751-6.

Zhu W, Cadet P, Mantione KJ, Kream RM, Stefano GB. Response to Comment on human white blood cells synthesize morphine: CYP2D6 modulation. J Immunol. 2006;176:5704.

Zhu W, Mantione KJ, Shen L, Stefano GB. In vivo and in vitro L-DOPA and reticuline exposure increases ganglionic morphine levels. Med Monit Sci. 2005;11:MS1-5.

Zhu W, Mantione KJ, Kream RM, Stefano GB. Alcohol-, nicotine-, and cocaine-evoked release of morphine from human white blood cells: Substances of abuse action converge on endogenous morphine release. Med Sci Monit. 2006;12:BR350-4.

Zhu W, Mantione KJ, Casares FM, Cadet P, Kim JW, et al. Alcohol-, nicotine-, and cocaine-evoked release of morphine from invertebrate ganglia: model system for screening drugs of abuse. Med Sci Monit. 2006;12:BR155-61.

Kosterlitz HW. Biosynthesis of morphine in the animal kingdom. Nature. 1987;330:606.

Kosterlitz HW. Has morphine a physiological function in the animal kingdom? Nature. 1985;317:671-2.

Stefano GB. Advances in endogenous morphine. Med Sci Monit. 2005;11:ED1-1.

Krueger H, Eddy NB, Sumwalt M. The pharmacology of the opium alkaloids. Publ Health Rep. 1941 Suppl 165: 2 vols. 1-1448, CXL.

Kilduff TS, Krilowicz B, Milsom WK, Trachsel L, Wang LC. Sleep and mammalian hibernation: homologous adaptations and homologous processes? Sleep. 1993;16:372-86.

Blass EM, Fitzgerald E. Milk-induced analgesia and comforting in 10-day-old rats: opioid mediation. Pharmacol Biochem Behav. 1988;29:9-13.

Wittels B, Scott DT, Sinatra RS. Exogenous opioids in human breast milk and acute neonatal neurobehavior: a preliminary study. Anesthesiology. 1990;73:864-9.

Max B. This and that: an artefactual alkaloid and its peptide analogs. Trends Pharmacol Sci. 1992;13:341-5.

Haavik J, Tosta K. Tyrosine hydroxylase and Parkinson´s disease. Mol Neurobiol. 1998;16:285-309.

Kupers R, Kehlet H. Brain imaging of clinical pain states: a critical review and strategies for future studies. Lancet Neurol. 2006;5:1033-44.

Salamon E, Esch T, Stefano GB. Pain and relaxation (review). Int J Mol Med. 2006;18:465-70.

Guarna M, Bianchi E, Bartolini A, Ghelardini C, Galeotti N, Bracci L, et al. Endogenous morphine modulates acute thermonociception in mice. J Neurochem. 2002;80:271-7.

Guarna M, Ghelardini C, Galeotti N, Stefano GB, Bianchi E. Neurotransmitter role of endogenous morphine in CNS. Med Sci Monit. 2005;11:RA190-3.

Parkinson J. An essay on the shaking palsy. Sherwood, Neely, Jones. London, 1817. reprinted in J Neuropsychiatry Clin Neurosci. 2002;14:223-36.

Goetz CG. Charcot on Parkinson´s disease. Mov Disord. 1986;1:27-32.

Hoehn M, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17:427-42.

Poewe W, Gerstenbrand F. Klinische Subtypen der Parkinson-Krankheit. Wien Med Wochenschr. 1986;136:384-7.

Poewe W. The need for neuroprotective therapies in Parkinson´s disease: a clinical perspective. Neurology. 2006;66:S2-9.

Kotake Y, Tasaki Y, Makino Y, Ohta S, Hirobe M. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF. J Neurochem. 1995;65:2633-8.

Kotake Y, Yoshida M, Ogawa M, Tasaki Y, Hirobe M, Ohta S. Chronic administration of 1-benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous amine in the brain, induces parkinsonism in a primate. Neurosci Lett. 1996;217:69-71.

Caparros-Lefevbre D, Eibaz A. Caribbean parkinsonism study group. Possible relation of atypical parkinsonism in the French West Indies with consumption of tropical plants: a case control study. Lancet. 1999;354:281-6.

Kotake Y, Okuda K, Kamizono M, Matsumoto N, Tanahashi T, Hara H, et al. Detection and determination of

reticuline and N-methylcocularine in the annonaceae family using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;806:75-8.

Lannuzel A, Michel PP, Caparros-Lefebvre D, Abaul J, Hocquemiller R, Ruberg M. Toxicity of Annonaceae for dopaminergic neurons: potential role in atypical parkinsonism in Guadeloupe. Mov Disord. 2002;17:84-90.

Antkiewicz-Michaluk L, Krygowska-Wajs A, Szczudlik A, Romañska I, Vetulani J. Increase in salsolinol level in the cerebrospinal fluid of parkinsonian patients is related to dementia: advantage of a new high-performance liquid chromatography method. Biol Psychiatry. 1997;42:514-8.

Collins MA. Alkaloids, alcohol and Parkinson's disease. Parkinsonism Relat Disord. 2002;8:417-22.

Byles J, Young A, Furuya H, Parkinson L. A drink to healthy aging: The association between older women's use of alcohol and their health-related quality of life. J Am Geriatr Soc. 2006;54:1341-7.

Pearce LA, Waterbury LD. L-methionine: a possible levodopa antagonist. Neurology.1974;24:840-1.

Charlton CG, Crowell B Jr. Parkinson´s disease-like effects of S-adenosyl-L-methionine: effects of L-DOPA. Pharmacol Biochem Behav. 1992;43:423-31.

Charlton CG, Mack J. Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain. Support for an excess methylation hypothesis for parkinsonism. Mol Neurobiol. 1994;9:149-61.

Charlton CG, Crowell B Jr. Effects of dopamine metabolites on locomotor activity and on the binding of dopamine: relevance to the side efects of L-dopa. Life Sci. 2000,66:2159-71.

Gluck MR, Zeevalk GD. Inhibition of brain mitochondrial respiration by dopamine and its metabolites: implications for Parkinson's disease and catecholamine-associated diseases. J Neurochem. 2004;91:788-95.

Lasala JM, Coscia CJ. Accumulation of a tetrahydroisoquinoline in phenylketonuria. Science. 1979;203:283-4.

Barbeau A. The «pink spot», 3,4-dimethoxyphenylethylamine and dopamine. Relationship to Parkinson's disease and to schizophrenia. Rev Can Biol. 1967;26:55-79.

Boulton AA, Pollitt RJ, Majer JR. Identity of a urinary «pink spot» in schizophrenia and Parkinson's disease. Nature.1967;215:132-4.

Williams AC, Ramsden DB. Autotoxicity, methylation and a road to the prevention of Parkinson´s disease. J Clin Neurosci. 2005;12:6-11.

Matsubara K, Aoyama K, Suno W, Awaya T. N-methylation underlying Parkinson´s disease. Neurotoxicol Teratol. 2002;24:593-8.

Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM et al. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res. 1979;1:249-54.

Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic parkinsonisms in humans due to a product of meperidine-analog synthesis. Science. 1983;239:979-80.

Simola N, Morelli M, Carta AR. The 6-hydroxydopamine model of Parkinson´s disease. Neurotox Res. 2007;11:151-67.

Hoglinger GU, Oertel WH, Hirsch EC. The rotenone model of parkinsonism-the five years inspection. J Neural Transm Suppl. 2006;(70):269-72.

Dinnis-Oliveira RJ, Remiao F, Carmo H, Duarte JA, Sánchez Navarro A, Bastos ML, et al. Paraquat exposure as an etiological factor of Parkinson´s disease. Neurotoxicol. 2006;27:1110-22.

Mena MA, de Yebenes JG. Drug-induced parkinsonism. Expert Opin Drug Saf. 2006;5:759-71.

Lee JJ, Kim YM, Park HD, Kang MH, Hong JT, Lee MK. Aggravation of L-DOPA-induced neurotoxicity by tetrahydropapaveroline in PC12 cells. Biochem Pharmacol. 2003;66:1787-95.

Banati RB, Blunt S, Graeber MB. What does apoptosis have to do with Parkinson´s disease. Mov Disord. 1999;14:384-5.

Hirsch EC, Hunot S, Faucheux B, Agid Y, Mizuno Y, Mochizuki H et al. Dopaminergic neurons degenerate by apoptosis in Parkinson´s Disease. Mov Disord. 1999;14:383-4.

BenderA, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, et al. High level of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet. 2006;38:515-7.

Arai R, Horiike K, Hasegawa Y. Dopamine-degrading activity of monoamino oxidase is not detected in the

neurons of the substantia nigra pars compacta of the rat. Brain Res. 1998;812:275-82.

Cohn RM, Roth KS. Hyperammonemia, bane of the brain. Clin Pediatr. 2004;43:893-9.

Cohen G. The pathobiology of Parkinson´s disease: biochemical aspects of dopamine neuron senescence. J Neural Transm Suppl. 1983;(19):89-103.

Riederer P, Konradi C, Hebenstreit Youdim MBH. Neurochemical perspectives to the function of monoamine oxidase. Acta Neurol Scand. 1989;126:41-5.

Forman MS, Lee VM, Trojanowski JQ. Nosology of Parkinson´s disease: looking for the way out of a quackmire. Neuron. 2005;47:479-82.

Abeliovich A, Beal MF. Parkinson genes: culprits and clues. J Neurochem. 2006;99:1062-72.

Fung HC, Scholz S, Matarin M, Simón-Sánchez J, Hernández D, Britton A, et al. Genome-wide genotyping in Parkinson´s disease and neurologically normal controls; first stage analysis and public release of data. Lancet Neurology. 2006;5:911-6.

Chan DK, Lam MK, Wong R, Hung WT, Wilcken DE. Strong association between N-acetyltransferase 2 genotype and PD in Hong Kong Chinese. Neurology. 2003;60:1002-5.

Rocca WA, Maraganore DM, Benedetti MD. Smoking, alcohol, and coffee consumption preceding Parkinson's disease. Neurology. 2001;56:984-5.

Deleu D. Smoking, alcohol, and coffee consumption preceding Parkinson's disease. Neurology. 2001;56:984.

Hernan MA, Chen H, Schwarzschild MA, Ascherio A. Alcohol consumption and the incidence of Parkinson's disease. Ann Neurol. 2003;54:170-5.

Benedetti MD, Bower JH, Maraganore DM, McDonnell SK, Peterson BJ, Ahlskog JE, et al. Smoking, alcohol, and coffee consumption preceding Parkinson's disease: a case-control study. Neurology. 2000;55:1350-8.

Logroscino G, Sesso HD, Paffenbarger RS Jr, Lee IM. Physical activity and risk of Parkinson's disease: a prospective cohort study. J Neurol Neurosurg Psychiatry. 2006;77:1318-22.

Abbott RD, Ross GW, White LR, Nelson JS, Masaki KH, Tanner CM, et al. Midlife adiposity and the future risk of Parkinson's disease. Neurology.. 2002;59:1051-7.

Park M, Ross GW, Petrovitch H, White LR, Masaki KH, Nelson JS et al. Consumption of milk and calcium in midlife and the future risk of Parkinson disease. Neurology. 2005;64:1047-51.

Becker G, Muller A, Braune S, Buttner T, Benecke R, Greulich W, et al. Early diagnosis of Parkinson´s disease. J Neurol. 2002;249 Suppl3:III/40-8.

Abbott RD, Ross GW, White LR, Tanner CM, Masaki KH, Nelson JS, et al. Excessive daytime sleepiness and subsequent development of Parkinson disease. Neurology. 2005;65:1442-6.

Abe K, Saitoh T, Horiguchi Y, Utsunomiya I, Taguchi K. Synthesis and neurotoxicity of tetrahydroisoquinoline derivatives for studying Parkinsons´s disease. Biol Pharm Bull. 2005;28:1355-62.

Todes CJ, Lees AJ. The pre-morbid personality of patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1985;48:97-100.

Mayeux R, Stern Y, Williams JB, Cote L, Frantz A, Dyrenfurth I. Clinical and biochemical features of depression in Parkinson's disease. Am J Psychiatry. 1986;143:756-9.

Shiba M, Bower JH, Maraganore DM, McDonnell SK, Peterson BJ, Ahlskog JE, et al. Anxiety disorders and depressive disorders preceding Parkinson's disease: a case-control study. Mov Disord. 2000;15:669-77.

Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins GT, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan. Mov Disord. 2007;22:41-7.

Schrag A, Barone P, Brown RG, Leentjens AF, McDonald WM, Starkstein S, et al. Depression rating scales in Parkinson's disease: critique and recommendations. Mov Disord. 2007;22:1077-92.

Marinus J, Viser M, Martínez-Martín P, van Hilten JJ, Stiggelbout A. A short psychosocial questionnaire for patients with Parkinson´s disease: the SCOPA-PS. J Clin Epidemiol. 2003;56:61-7.

Marinus J, Visser M, Stiggelbout AM, Rabey JM, Martinez-Martin P, Bonuccelli U, et al. A short scale for the assessment of motor impairments and disabilities in Parkinson's disease: the SPES/SCOPA. J Neurol Neurosurg Psychiatry. 2004;75:388-95.

Martinez-Martin P, Cubo-Delgado E, Aguilar-Barbera M, Bergareche A, Escalante S, Rojo A, et al. Estudio piloto sobre una medida específica para los trastornos del sueño de la enfermedad de Parkinson SCOPA-sueño. Rev Neurol. 2006;43:577-83

Ferreira JJ, Desboeuf K, Galitzky M, Thalamas C, Brefel-Courbon C, Fabre N, et al. Sleep disruption, daytime somnolence and ‘sleep attacks' in Parkinson's disease: a clinical survey in PD patients and age-matched healthy volunteers. Eur J Neurol. 2006;13:209-14.

Gjerstad MD, Alves G, Wentzel-Larsen T, Aarsland D, Larsen JP. Excessive daytime sleepiness in Parkinson disease: is it the drugs or the disease? Neurology. 2006;67:853-8.

Fabbrini G, Barbanti P, Aurilia C, Vanacore N, Pauletti C, Meco G. Excessive daytime sleepiness in de novo and treated Parkinson´s disease. Mov Disord. 2002;17:1026-30.

Hely MA, Morris JG, Traficante R. O´Sullivan DJ, Williamson PM. The Sydney Multicenter Study of Parkinson's disease: progression and mortality at 10 years. J Neurol Neurosurg Psychiatry. 1999;67:300-7.

Poewe W. The need for neuroprotective therapies in Parkinson´s disease: a clinical perspective. Neurology 2006;66:S2-9.

Brocks DR. Anticholinergic drugs used in Parkinson's disease: An overlooked class of drugs from a pharmacokinetic perspective. J Pharm Pharm Sci. 1999;2:39-46.

Degkwitz R, Frowein R, Kulenkampff C, Mohs U. On the effects of L-dopa in the man and their modification by reserpine, chlorpromazine, iproniazide and vitamin B6. Klin Wochenschr. 1960;38:120-3.

Birkmayer W, Hornykiewicz O. Der L-3,4-dioxyphenylalanin (DOPA)-Effect bei der Parkinson-Akinese. Wien Klin Wochenschr. 1961;73:787-8.

Barbeau A. L-Dopa therapy in Parkinson´s disease. A critical review of nine years experience. Can Med Assoc J. 1969;101:791.80.

Fahn S, and the Parkinson Study Group. Does levodopa slow or hasten the rate of progression of Parkinson's disease? J Neurol. 2005;252 Suppl 4:IV37-IV42.

Hoehn MM, Rutledge CO. Acute overdose with levodopa. Neurology. 1975;25:792-4.

Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson´s disease. New Engl J Med. 1989;321:1364-71.

Landau WM. Clinical neuromythology IX. Pyramid sale in the bucket shop: DATATOP bottoms out. Neurology. 1990;40:1337-9.

Berg D, Becker G, Reiners K. Reduction of diskynesia and induction of akynesia induced by morphine in two parkinsonian patients with severe sciatica. J Neural Transm. 1999;106:725-8.

Berg D, Becker G, Naumann M, Reiners K. Morphine in tardive and idiopathic dystonia (short communication). J Neural Transm. 2001;108:1035-41.

Ferreira JJ, Galitzky M, Montastruc JL, Rascol O. Sleep attacks and Parkinson´s disease treatment. Lancet. 2000;355:1333-4.

Lauterbach EC. The neuropsychiatry of Parkinson's disease and related disorders. Psychiatr Clin North Am. 2004;27:801-25.

Brefel-Courbon C, Payoux P, Thalamas C, Ory F, Quelven I, Chollet F, et al. Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study. Mov Disord. 2005;20:1557-63.

Denny-Brown D. Paralysis Agitans. In Cecil Textbook of Medicine. Philadelphia: Saunders; 1964. p.1605-8.

Cohen G, Pasik P, Cohen B, Leist A, Mytilineou C, Yahr MD. Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in monkeys. Eur J Pharmacol. 1984;106:209-10.

Factor SA, Sánchez-Ramos JR, Weiner WJ. Vitamin E therapy in Parkinson´s disease. Adv Neurol. 1990;53:457-60.

Riley D, Lang AE. Practical application of a low-protein diet for Parkinson´s disease. Neurology. 1988;38:1026-31.

Pincus JH, Barry KM. Protein redistribution diet restores motor function in patients with dopa-resistant "off" periods. Neurology. 1988;38:481-3.

Lang AE. Neuroprotection in Parkinson´s disease: and now for something completely different? Lancet Neurology. 2006;5:990-1.

Olanow CW, Schapira AHV, LeWitt PA, Kieburtz K, Sauer D, Olivieri G, et al. TCH346 as a neuroprotective

drug in Parkinson´s disease: a double blind, randomised, controlled trial. Lancet Neurol. 2006;5:1013-20.

Waldmeier P, Bozyczko-Coyne D, Williams M, Vaught JL. Recent clinical failures in Parkinson´s disease with apoptosis inhibitors underline the need for a paradigm shift in drug discovery for neurodegenerative diseases. Biochem Pharmacol. 2006;72:1197-206.

DeKosky ST, Marek K. Looking backward to move forward: early detection of neurodegenerative disorders. Science. 2003;302:830-4.

Berendse HW, Ponsen MM. Detection of preclinical Parkinson´s disease along the olfactory tract. J Neural Transm Suppl. 2006;(70):321-5.

Siderowf A, Stern MB. Preclinical diagnosis of Parkinson´s disease: are we there yet? Curr Neurol Neurosci Rep. 2006;6:295-301.

Antkiewicz-Michaluk L. Endogenous risk factors in Parkinson´s disease: dopamine and tetrahydroisoquinolines. Pol J Pharmacol. 2002;54:567-72.

Esch T. Kim JW, Stefano GB. Neurobiological implications of eating healthy. Neuro Endocrinol Lett. 2006;27:21-33.

Stefano GB. Endogenous morphine: a role in wellness medicine. Med Sci Monit. 2004;10:ED5.

Marsden CD. Parkinson´s disease. Lancet. 1990;335:948-52.

McNaught KS, Carrupt PA, Altomare C, Cellamare S, Carotti A, Testa B, et al. Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson´s disease. Biochem Pharmacol. 1998;56:921-33.

Kurup RK, Kurup PA. Hypothalamic digoxin-mediated model for Parkinson's disease. Int J Neurosci. 2003;113:515-36.

Arun P, Ravikumar A, Leelamma S, Kurup PA. Endogenous alkaloids in the brain of rats loaded with tyrosine/ tryptophan & in the serum of patients of neurodegenerative & psychiatric disorders. Ind J Med Res. 1998;107:231-8.

Bosch ME, Sánchez AR, Rojas FS, Ojeda CB. Morphine and its metabolites: analytical methodologies for its determination. J Pharm Biomed Anal. 2007;43:799-815.

Zhu W, Baggerman G, Goumon Y, Casares F, Brownawell B, Stefano GB. Presence of morphine and morphine-6-glucuronide in the marine mollusk Mytilus edulis ganglia determined by GC/MS and Q-TOF-MS. Starvation increases opiate alkaloid levels. Brain Res Mol Brain Res. 2001;88:155-60.

Filippi L, Manni C, Pierantozzi M, Brusa L, Danieli R, Stanzione P, et al. 123I-FP-CIT in progressive supranuclear palsy and in Parkinson's disease: a SPECT semiquantitative study. Nucl Med Commun. 2006;27:381-6.

Marshall VL, Patterson J, Hadley DM, Grosset KA, Grosset DG. Successful antiparkinsonian medication withdrawal in patients with Parkinsonism and normal FP-CIT SPECT. Mov Disord. 2006;21:2247-50.

Matsui H, Nishinaka K, Oda M, Hara M, Komatsu K, Kubori T, et al. Excessive daytime sleepiness in Parkinson disease: a SPECT study. Sleep. 2006;29:917-20.

Zhu BT. CNS dopamine oxidation and catechol-O-methyltransferase: importance in the etiology, pharmacotherapy, and dietary prevention of Parkinson´s disease. Int J Mol Med. 2004;13:343-53.

Perea-Sasiaín J. Reflexiones sobre la biosíntesis de la morfina y el Parkinson idiopático. Rev Salud Pública. 2007;9:308-14.

Gómez González J. Bodas de oro profesionales (1955-2005) Promoción 1955. Facultad de Medicina, Universidad Nacional de Colombia. Medellín: Universidad Cooperativa de Colombia; 2005.

Visitas a la página del resumen del artículo

596

Descargas

Los datos de descarga aún no están disponibles.

Cómo citar

Perea Sasiaín, J. (2008). Biosíntesis de la morfina: su importancia en la enfermedad de Parkinson. Revista De La Facultad De Medicina, 56(2), 161-189. https://revistas.unal.edu.co/index.php/revfacmed/article/view/15923

Licencia

Derechos de autor 2008 Revista de la Facultad de Medicina

Creative Commons License

Esta obra está bajo una licencia Creative Commons Reconocimiento 3.0 Unported.

-