Cinqüenta anos demedicamentosantipsicóticos empsiquiatria

Cinqüenta anos demedicamentosantipsicóticos empsiquiatria

(Parte 7 de 10)

110. Naassila M, Legrand E, d'Alche-Biree F, Daoust M
Pharmacogenetics 1996; 6(5):449-57
patients. Can Med Assoc J 1983; 128(8):894, 897

Photosensitized cross-linking of erythrocyte membrane proteins. Chem Biol Interact 1983; 4(3):275-87. 106. Merville MP, Decuyper J, Piette J, Calberg-Bacq CM, Van de Vorst A. In vitro cross-linking of bovine lens proteins photosensitized by promazines. Invest Ophthalmol Vis Sci 1984; 25(5):573-80. 107. Mitchell AC, Brown KW. Chlorpromazine-induced retinopathy. Br J Psychiatry 1995; 166(6):822-3. 108. Moyes DG. Malignant hyperpyrexia caused by trimeprazine. Case report. Br J Anaesth 1973; 45(1):163-4. 109. Mutlu N, Ozkurkcugil C, Culha M, Turkan S, Gokalp A. Priapism induced by chlorpromazine. Int J Clin Pract 1999; 53(2):152-3. Cyamemazine decreases ethanol intake in rats and convulsions during ethanol withdrawal syndrome in mice. Psychopharmacology (Berl) 1998; 140(4):421-8. 1. Nakamura K, Yokoi T, Inoue K, Shimada N, Ohashi N, Kume T, Kamataki T. CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes. 112. Nielsen FE, Nielsen SL, Knudsen F, Lyngborg K. Levomepromazine (Nozinan) and pain therapy in acute myocardial infarction. Ugeskr Laeger 1989; 151(32):2048. 113. Nordenberg J, Fenig E, Landau M, Weizman R, Weizman A. Effects of psychotropic drugs on cell proliferation and differentiation. Biochem Pharmacol 1999; 58(8):1229-36. 114. Novo JL, Menegoci JC, Balsamo SB, Rozas A, Neme B. Experiência clínica com o uso de uma clorofenotiazinilescopina-levomepromazina-metilbutifereniodipirona no trabalho de parto. Matern Infanc (Sao Paulo) 1970; 29(4):425-9. 115. Oftsti E. Alimemazine (Vallergan) an alternative to traditional hypnotic drugs. Tidsskr Nor Laegeforen 1975; 95(31):1796-7. 116. Olsen AK, Pedersen JE, Banning AM. Inhalation of levopromazine (Nozinan) in the treatment of status asthmaticus. Ugeskr Laeger 1995; 157(26):3770-1. 117. Ortiz MFB, Santo-Domingo CJ. Treatment of pain in burn patients. Arch Neurobiol (Madr) 1984; 47(2):73-84. 118. Parrott AC, Wesnes K. Promethazine, scopolamine and cinnarizine: comparative time course of psychological performance effects. Psychopharmacology (Berl) 1987; 92(4):513-9. 119. Patt RB, Proper G, Reddy S. The neuroleptics as adjuvant analgesics. J Pain Symptom Manage 1994; 9(7):446- 53. 120. Pedersen JE, Olsen A, Banning A. Inhalation of levomepromazine in severe acute asthma. Lancet 1994; 344(8929):1095-6. 121. Peters WJ, Friedman J. Methotrimeprazine for burn 122. Pies RW. Handbook of Essential Psychopharmacology. American Psychiatric Press, Washington, 1998. 35. Price EJ, Venables PJ. Drug-induced lupus. Drug Saf 1995; 12(4):283- 90. 123. Plant JR, MacLeod DB. Response of a promethazineinduced coma to flumazenil. Ann Emerg Med 1994; 24(5):979- 82. 124. Price EJ, Venables PJ - Drug-induced lupus. Drug Saf 12(4):283-90, 1995. 125. Puttick N, Van der Walt JH. The effect of premedication on the incidence of postoperative vomiting in children after E.N.T. surgery. Anaesth Intensive Care 1987; 15(2):158-62. 126. Rager P, Cosculluela D, Deviers D. Drug hepatitis. Possible role of cyamemazine Presse Med 1983; 12(31):1941. 127. Rasheed A, Javed MA, Nazir S, Khawaja O. Interaction of chlorpromazine with tricyclic anti-depressants in

Isobe A, Satoh T. Inflammatory activity ofpolymeric

schizophrenic patients. JPMA J Pak Med Assoc 1994; 4(10):233-4. 128. Remy AJ, Larrey D, Pageaux GP, Ribstein J, Ramos J, Michel H. Cross hepatotoxicity between tricyclic antidepressants and phenothiazines. Eur J Gastroenterol Hepatol 1995; 7(4):373-6. 129. Rico H, Gomez M, Revilla M, Gonzalez-Riola J, Seco C, Hernandez ER, Villa LF, Gervas J. Effects of promethazine on bone mass and on bone remodeling in ovariectomized rats: A morphometric, densitometric, and histomorphometric experimental study. Calcif Tissue Int 1999; 65(4):272-5. 130. Roelofse JA, Louw LR, Roelofse PG. A double blind randomized comparison of oral trimeprazine-methadone and ketamine-midazolam for sedation of pediatric dental patients for oral surgical procedures. Anesth Prog 1998; 45(1):3-1. 131. Roy S, Noblet C, Fillastre JP, Godin M, Joly P, Lauret P, Francois A, Hemet J. Acute interstitial granulomatous nephropathy secondary to the administration of a phenothiazine: cyamemazine. Nephrologie 1994; 15(3):265-6. 132. Royer P, Tonnel M, Galland S, Dormagen C. Mepronizine and insomnia. Ann Med Nancy 1965; 4:650-7. 133. Salhab AS, Dujovne CA. Toxicity of promazine and chlorpromazine to isolated rat hepatocytes and its modification by liposome entrapment. Pharmacology 1986; 3(6):311-21. 134. Saller R, Hellenbrecht D. Benefit and risk of high-dose metoclopramide in comparison to high-dose haloperidol or triflupromazine in cisplatin-induced vomiting. Klin Wochenschr 1985; 63(9):428-32. 135. Sampaio N. A clorpromazina em psiquiatria. Bol Hosp Jul Mor 1955; 4:5. 136. Sauvage MF, Rousseau A, Marquet P, Dumeirain F, Raby C, Lachatre G. In vitro and in vivo study of the antithyroid side effects of trimeprazine. Toxicol Appl Pharmacol 1999; 158(2):125-31. 137. Schanda H, Presslich O, Hermann P, Walcher R. Inpatient withdrawal treatment of heroin addicts with neuroleptics. Wien Klin Wochenschr 1982; 94(2):43-8. 138. Schwinghammer TL, Kroboth FJ, Juhl RP. Extrapyramidal reaction secondary to oral promethazine. Clin Pharm 1984; 3(1):83-5. 139. Seeman P, Tallerico T. Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors. Mol Psychiatry 1998; 3(2):123-34. 140. Sep-Kowalik B. Theralene as an antipsychotic drug in the light of our clinical observations. Neurol Neurochir Psychiatr Pol 1966; 16(10):1173-7. 141. Sgaragli G, Ninci R, Della Corte L, Valoti M, Nardini M, Andreoli V, Moneti G. Promazine. A major plasma metabolite of chlorpromazine in a population of chronic schizophrenics. Drug Metab Dispos 1986; 14(2):263-6. 142. Shawn DH, McGuigan MA. Poisoning from dermal absorption of promethazine. Can Med Assoc J 1984;130(1):1460-1 143. Shepherd M, Lader M, Rodnight R. Psicofarmacologia Clinica. Trad espan, Ed Acribia, Saragoça, 1972. 144. Shigehara N, Kakegawa H, Miyataka H, Matsumoto H, photoproducts of chlorpromazine. Biol Pharm Bull 1993; 16(6):576-8. 145. Shin JG, Soukhova N & Flockhart DA. Effect of antipsychotic drugs on human liver cytochrome P-450 (CYP) isoforms in vitro: preferential inhibition of CYP2D6. Drug Metab Dispos 1999; 27(9):1078-84. 146. Simonoff EA, Stores G. Controlled trial of trimeprazine tartrate for night waking. Arch Dis Child 1987; 62(3):253-7. 147. Stiell IG, Dufour DG, Moher D, Yen M, Beilby WJ, Smith NA. Methotrimeprazine versus meperidine and dimenhydrinate in the treatment of severe migraine: a

H, Ahola V, Dahl ML, Salokangas RKCitalopram causes no

randomized, controlled trial. Ann Emerg Med 1991; 20(1):1201-5. 148. Stowell LI. Suicide with the veterinary drug acepromazine. J Anal Toxicol 1998; 2(2):166-8. 149. Subra G, Noyer J, Legros P. Study of a non-barbiturate hypnotic "FH 040-3" (mepronizine) in a psychiatric setting. Encephale 1967; 56(5):469-79. 150. Sundberg R, Ar'Rajab A, Ahren B. Improved liver preservation with UW solution by chlorpromazine donor pretreatment. Transplant Proc 1990; 2(2):508. 151. Svenson KA. Pharmacological characterization of dopamine D3 and D4 receptor ligands. European Neuropsychopharmacology 1997; 7(1002):S121-S122. 152. Sykes AJ, Kiltie AE, Stewart AL. Ondansetron versus a chlorpromazine and dexamethasone combination for the prevention of nausea and vomiting: a prospective, randomised study to assess efficacy, cost effectiveness and quality of life following single-fraction radiotherapy. Support Care Cancer 1997; 5(6):500-3. 153. Sykes NP, Oliver DJ. Isotonic methotrimeprazine by continuous infusion in terminal cancer care. Lancet 1987; 1(8529):393-4. 154. Syrek M, Wojcikowski J, Daniel W. Effect of carbamazepine on the pharmacokinetics of promazine. Pol J Pharmacol 1996; 48(6):601-8. 155. Syrek M, Wojcikowski J, Daniel WA. Promazine pharmacokinetics during concurrent treatment with tricyclic antidepressants. Pol J Pharmacol 1997; 49(6):453-62. 156. Syvalahti EK, Taiminen T, Saarijarvi S, Lehto H, Niemi significant alterations in plasma neuroleptic levels in schizophrenic patients. J Int Med Res 1997; 25(1):24-32. 157. Takorabet L, Ropars A, Stasiuk L, Raby C, Charreire J. Phenothiazine-induced increasein thyroid autoantigens and costimulatory molecules on thyroid cells: a pathophysiological mechanism for drug-induced autoimmunity? Clin Exp Immunol 1998; 1(2):415-21. 158. Tishler PV. The effect of therapeutic drugs and other pharmacologic agents on activityof porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria.Life Sci 1999; 65(2):207-14. 159. Tokunaga H, Kudo K, Imamura T, Jitsufuchi N, Ohtsuka Y, Ikeda N. Plasma concentrations of antipsychotic drugs in psychiatric inpatients. Nippon Hoigaku Zasshi 1997; 51(6):417-2. 160. Tokunaga Y, Wicomb WN, Concepcion W, Nakazato P, Collins GM, Esquivel CO. Successful 20-hour rat liver preservation with chlorpromazine in sodium lactobionate sucrose solution. Surgery 1991; 110(1):80-6. 161. Tracqui A, Kintz P, Jamey C, Mangin P. Toxicological data in a fatality involving cyamemazine. J Anal Toxicol 1993; 17(6):386-8. 162. Trichard C, Paillere-Martinot ML, Attar-Levy D, Recassens C, Monnet F, Martinot J. Binding of antipsychotic drugs to cortical 5-Ht2A receptors: a PET study of chlorpromazine, clozapine, and amisulpride in schizophrenic patients. Am J Psychiatry 1998; 155(4):505-8. 163. Tyan ML. Effect of promethazine on lumbar vertebral bone mass in postmenopausal women. J Intern Med 1993; 234(2):143-8. 164. Vandel S, Bertschy G, Baumann P, Bouquet S, Bonin B, Francois T, Sechter D, Bizouard P. Fluvoxamine and fluoxetine: interaction studies with amitriptyline, clomipramine and neuroleptics in phenotyped patients. Pharmacol Res 1995; 31(6):347-53. 165. Vilalta J, Treserra J, Garcia-Esteve L, Garcia-Giralt M, Cirera E. Methadone, clonidine and levomepromazine in the treatment of opiate abstinence syndrome: double-blind clinical trial in heroin-addicted patients admitted to a general hospital for organic pathology. Med Clin (Barc) 1987; 8(17):674-6.

166. Vizzotto S, Tomchinsky RB, Goes JF & Fiore LJ. Dados preliminares sobre os resultados obtidos com a clorpromazina em Psiquiatria (71 casos). Arq Dep Assist Psicop Est S Paulo, 1955; 21:234. 167. Voirol P, Robert PA, Meister P, Oros L, Baumann P. Psychotropic drug prescription in a psychiatric university hospital. Pharmacopsychiatry 1999; 32(1):29-37. 168. Wang CK, Liu JD, Lin SY, Liao LY, Cheng NY, Wang CS, Siauw CP, Chen PH. Drug-induced liver disease--a review of 14 cases. Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 1995; 1(4):213-9. 169. Warnes H, Lehmann HE, Ban TA. Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases. Can Med Assoc J 1967; 96(15):1112-3. 170. Wasfy A. Attempt at a study of the effect of aminopromazine (3828 RP) on uterine cervix dilation. Gynecol Obstet (Paris). 1968 Nov-Dec;67(5):553-8.. 171. Wasfy A. Combination in perfusion of a spasmolytic phenothiazine derivative (aminopromazine) and oxytocics in hemorrhage from low insertion of the placenta. Gynecol Obstet (Paris). 1967 Sep-Oct;6(4):483-8. 172. Wik G. Effects of neuroleptic treatment on cortisol and 3- methoxy-4-hydroxyphenylethyl glycol levels in blood. J Endocrinol 1995; 144(3):425-9. 173. Wolf ME, Richer S, Berk MA, Mosnaim AD. Cutaneous and ocular changes associated with the use of chlorpromazine. Int J Clin Pharmacol Ther Toxicol 1993; 31(8):365-7. 174. Yamauchi K, Baba K, Ikegami N, Miyaoka H, Kamijima K. A survey of drug utilization in psychiatric hospitals in Japan: the basic analysis of the current status of prescription patterns. Seishin Shinkeigaku Zasshi 1998; 100(1):51-68.

B) Fenotiazinas Piperazínicas

nematóides em nosso meio

A piperazina é substância ainda hoje empregada como um eficaz vermífugo que age por bloqueio da atividade neuromuscular no Ascaris lumbricoides e Enterobius vermicularis, dois parasistas comuns nas infestações por

antipsicótica e efeitos extrapiramidais acentuados

As fenotiazinas piperazínicas têm um perfil de efeitos adversos diferente das alifáticas. Causam menos sedação e hipotensão, têm efeitos anticolinérgicos muito fracos, mas são potentes bloqueadores dopaminérgicos centrais (de potência intermediária a alta), com ação


O perfil do grupo assemelha-se muito ao de butirofenonas com fraca ação alfadrenérgica e

Nesta seção serão examinadas dezesseis substâncias pertencentes a este grupo com ação antipsicótica: acetofenazina, butaperazina, carfenazina, ciclofenazina, clorimpifenina, dixirazina, flufenazina, metofenazina, oxaflumazina, perazina, perfenazina, proclorperazina, tietilperazina, tiopropazato, tioproperazina e trifluperazina.

Destas, apenas encontram-se em comercialização como antipsicóticos no Brasil a flufenazina (cloridrato para uso oral e enantato, para aplicações intramusculares de depósito:


DÉPÔT , FLUFENAN DÉPÔT ) e trifluoperazina (dicloridrato, para uso oral:

STELAZINE)No passado já foram aqui

comercializadas a perfenazina (em associação com a amitriptilina, MUTABON ) e a tioproperazina (MAJEPTIL ), este último um potente neuroléptico recomendado exclusivamente para uso hospitalar.

10-{3-[4-(2-hidroxietil)-1-piperazinil]-propil}- fenotiazin-2-il maleato de metilcetona ou:

Etanona, 1-(10-(3-(4-(2-hidroxietil)-1- piperazinil)propil)-10H-fenotiaz-in-2-il)- ou: 2-Acetil-10-(3-(4-(2- hidroxietil)piperazinil)propil)-10H-fenot-iazina dimaleato ou:

Cetona, 10-(3-(4-(2-hidroxietil)-1- piperazinil)propil)fenotiazin-2-il metil, dimaleato ou:

Cetona, 10-(3-(4-(2-hidroxietil)-1- piperazinil)propil)fenotiazin-2-il metil, maleato (1:2) (sal) ou: (SCH 6673). (CAS RN 2751-68-0, base; 5714-0-1, dimaleato).

D: 20 a 40mg; 40 a 80mg (53, 262).

Antipsicótico típico de potência intermediária com poucos efeitos autonômicos e perfil muito semelhante ao da perfenazina.

efeitos extrapiramidais em geral

Os efeitos adversos mais comuns, como quase todos os demais derivados fenotiazínicos piperazínicos, incluem fadiga, sonolência, ganho de peso, convulsões, inquietude, tremores e

antipsicótico (40, 122)

Do mesmo modo que a perfenazina e a trifluoperazina, foi sugerida em doses baixas, como medicação coadjuvante nas depressões ansiosas (123) além do clássico emprego como

diferencial nesta indicação (53)
Foi muito utilizada no Canadá, onde até

Na antiga classificação dos neurolépticos da escola francesa, era incluída entre os neurolépticos “ativadores” e chegou a ser sugerida para uso em crianças e adolescentes autistas mas nunca se chegou a confirmar uma utilidade recentemente permanecia licenciada para uso humano.

Não disponível comercialmente no Brasil

No Exterior: TINDAL (Canadá) - dimaleato de, comp 20mg.

N-(gama-(4'-Metil-1'-piperazinil)propil)-3- butirilfenotiazina ou: 1-(10-(3-(4-Metil-1-piperazinil)-propil)-10H- fenotiazin-2-il)-- 1-butanona ou: 1-(10-(3-(4-Metil-1-piperazinil)propil)fenotiazin- 2-il)-1-buta- nona ou:

1-Butanona, 1-(10-(3-(4-metil-1- piperazinil)propil)-10H-fenotiazin-2-il)- ou: 1-Butanona 1-(10-(3-(4-metil-1- piperazinil)propil)fenotiazin-2-il)- ou:

(AHR-712)(Bayer 1362) (CAS RN 653-03-2 ).

FM: C24-H31-N3-O-S

Introduzida na década de 60 como boa parte dos antipsicóticos fenotiazínicos mais recentes. Como outras fenotiazinas piperazínicas, também foi aplicada em baixas doses como medicação ansiolítica alternativa (260), além do emprego como antipsicótico tanto na Esquizofrenia Crônica quanto Aguda (31, 51, 52, 95, 121, 147).

(Parte 7 de 10)