Pharmacological and Neuromodulatory Treatments for Panic Disorder: Clinical Trials from 2010 to 2018

OBJECTIVE: Treatment for panic disorder (PD) have evolved, although there is still a strong unmet need for more effective and tolerable options. The present study summarizes and discusses recent evidence regarding the pharmacological and neuromodulatory treatment of PD. METHODS: MEDLINE, Cochrane Library, PsycINFO and Thomson Reuters’s Web of Science were searched for clinical trials published between 2010 and 2018. We included all prospective experimental studies including randomized controlled trials (RCT) and other clinical trials with more than 10 patients. RESULTS: Only 11 articles met the inclusion criteria, including 4 RCT, 3 open clinical trials and 5 comparative clinical trials. RCT demonstrated efficacy of transcranial magnetic stimulation (TMS) in only one of two trials. Neither pindolol nor d-fenfluramine were effective in blocking flumazenil-induced panic attacks. Augmentation with quetiapine was not superior to placebo. Open trials indicated that escitalopram, vortioxetine and TMS may be effective. Comparative trials did not demonstrate superiority from any drug, but confirmed tranylcypromine, paroxetine, clonazepam and alprazolam as effective options. CONCLUSION: The current study confirmed the efficacy of tranylcypromine, paroxetine, clonazepam, alprazolam and escitalopram. Vortioxetine and TMS, with duration of 4 or more weeks, also seems to be effective. Quetiapine, pindolol and d-fenfluramine were not considered effective compounds.

Cardiovascular drugs in human mechanical nociception: digoxin, amlodipine, propranolol, pindolol and atenolol

Calcium channel blockers, β adrenergic receptor blockers and Na/K ATPase inhibitors are widely used drugs, mainly for cardiovascular diseases. Their pharmacological targets are not restricted to the cardivascular tissue, nociceptive system structures also express similar targets, which strongly suggests a direct effect on pain sensation. To evaluate the pain intensity changes in outpatient groups, who receive these drugs as a therapy, a cross-sectional sampled, randomized patient groups receiving the calcium channel blocker amlodipine for blood hypertension (n=45), β adrenergic receptor blockers (propranolol, atenolol or pindolol; n=40) for blood hypertension, or digoxin (n=40) for heart failure, were compared to an aparently healthy volunteers control group (n=60). A calibrated noxious pressure of 890 g/mm² was applied for 5 seconds on the patient’s sternum. Subjective pain intensity was reported by the visual analog scale (VAS, 0 to 10). Pain modulation system was evaluated by the application of a second stimulus with a 5 minutes delay. The analgesic effect of the β blockers group (propanolol, atenolol, pindolol) was dosage-dependant (-36.8 percent; P=0.0000003), without differences among them. The calcium channel blocker amlodipine showed lower pain scores (-50.6 percent; P=0.0000003) than β-receptor blockers (P=0.0000003). Digoxin presented the highest pain scores (+56.5 percent; P=0.0000003). All pain scores for the second stimulus were lower than the first stimulus and were differentially affected by β-blockers (atenolol, pindolol and propanolol) and calcium channel blocker (amlodipine), but not by digoxin. These results suggest the influence of widely clinically used cardiovascular drugs on nociception.

Los bloqueadores de los canales de calcio, los bloqueadores de los receptores β adrenérgicos y los inhibidores de la ATPasa Na/K son medicamentos ampliamente usados en enfermedades cardiovasculares. Sus blancos farmacológicos no se restringen al tejido cardiovascular, el sistema nervioso nociceptivo expresa blancos similares, lo que sugiere fuertemente un efecto directo en la sensación del dolor. El objetivo del presente estudio fue evaluar los cambios en la intensidad del dolor en grupos de pacientes ambulatorios que reciban estos medicamentos como terapia. Grupos aleatorios de pacientes que reciben el bloqueador de canales de calcio amlodipina contra la hipertensión arterial (n=45), bloqueadores de receptores β adrenérgicos (propranolol, atenolol or pindolol; n=40) contra la hipertensión arterial o digoxina (n=40) por insuficiencia cardíaca fueron comparados con un grupo control de voluntarios aparentemente sanos (n=60). A todos los grupos se les aplicó una presión nociva calibrada de 890 g/mm² durante 5 segundos sobre el esternón. El paciente reportó la intensidad subjetiva del dolor mediante la escala visual análoga (VAS). El sistema de modulación descendente del dolor fue evaluado mediante la aplicación del mismo estímulo 5 minutos después del primero. Se determinó un efecto analgésico en el grupo de β bloqueantes (propanolol, atenolol, pindolol) dosis dependiente (-36,8 por ciento; P=0,0000003) sin mostrar diferencias entre ellos. El bloqueador de canales de calcio amlodipina mostró un efecto analgésico (-50,6 por ciento; P=0,0000003) que fue mayor que el de los β bloqueantes (P=0,0000003). El grupo con digoxina expresó un efecto hiperalgésico (+56,5 por ciento; P=0,0000003). Todos los valores de dolor para el segundo estímulo fueron menores que para el primero y fueron diferencialmente afectados por los β bloqueantes (atenolol, pindolol and propanolol) y por la amlodipina pero no por la digoxina. Estos...

5-HT1A/1B receptors, alpha2-adrenoceptors and the post-receptor adenylate cyclase activation in the mice brain are involved in the antidepressant-like action of agmatine / 药学学报

This study is to explore the possible mechanisms of the antidepressant-like effect of agmatine. By using two traditional "behavior despair" model, tail suspension test and forced swimming test, we examined the effects of some monoamine receptor antagonists (including beta-adrenergic receptor antagonist propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol, alpha2-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3 receptor antagonist tropisetron) on the antidepressant-like action of agmatine in mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal cortex was determined by radioimmunoassay. Single dose of agmatine (5-40 mg x kg(-1), ig) dose-dependently decrease the immobility time in tail suspension test in mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg x kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2-adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4 mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20 mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1), ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg x kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5-10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1-6.4 micromol x L(-1)) with the synaptic membrane extracted from rat frontal cortex activated the AC in a dose-dependent manner in vitro. While the effect of agmatine (6.4 micromol x L(-1)) was dose-dependently antagonized by pindolol (1 micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(-1)) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.

Reducao do tempo de latencia para o efeito antidepressivo pela administracao de pindolol / Pindolol as a means to decrease the latency period to obtain antidepressant effect

Diferentes farmacos antidepressivos aumentam os niveis extracelulares de serotonina (5-HT) nos nucleos da rafe e do mesencefalo. Como resultado desse aumento, ocorre ativacao dos autoreceptores somatodendriticos 5-HT que, por mecanismo de feedback negativo, determina uma subsequente reducao na liberacao de 5-HT. Esse mecanismo tem sido implicado como uma das causas do retardo no inicio de acao dos inibidores da recaptacao de serotonina (ISRSs) apos sua administracao...

Involvement of dopamine D2 and 5-HT1A receptors in roxindole-induced antinociception.

Roxindole, a DA D2 receptor agonist (2-16 mg/kg) produced dose-dependent increase in percentage antinociception. The effect which was blocked by DA D2 antagonist (-)sulpiride (50 mg/kg) and 5-HT1A receptor antagonist (-) pindolol (5 mg/kg). Roxindole (4 and 8 mg/kg) reversed both naloxone (20 mg/kg)-induced hyperalgesia and reserpine (2 mg/kg)-induced hyperalgesia. This reversal was sensitive to blockade by both (-)sulpiride (50 mg/kg) and (-) pindolol (5 mg/kg). The present study suggests that roxindole-induced antinociception is mediated by postsynaptic DA D2 and 5-HT1A receptors.

Correlación entra la proliferación celular y la expresión de receptores beta adrenérgicos en linfocitos T activados / Relation between cell proliferation and beta adrenergic receptors expression in activated T lymphocytes

Se caracterizó la presencia de receptores (R)ß adrenérgicos em linfocitos murinos normales estimulados com Concanavalina A (Con A) y en una línea celular hiperproliferativa (BW5147) mediante la unión específica del radioligando 125Iodo-cianopindolol (125I/CYP)) a las células. La funcionalidad de los R se midió a través de cambios en la produccón de AMPc en presencia del agonista ß adrenérgico isoproterenol (ISO). Ambos tipos celulares mostraron un número disminuido de R ß adrenérgicos por unión específica al 125I-CYP. Se midieron los niveles intracelulares de AMPc en presencia de un agonista ß adrenérgico, las células BW5147 no mostraron un incremento significativo en los niveles de AMPc mientras que las células con Con A mostraron un incremento aunque menor al que presentan linfocitos normales, sin embargo, ambos tipos celulares respondieron a la prostaglandina E1(PGE1) produciendo un incremento en la produción de AMPc. Podemos concluir que la línea celular hiperproliferativa BW5147 no posee R funcionales, en este trabajo se analiza la posible implicancia de un camino intracelular alternativo y su control neuroendocrino

O uso de betabloqueadores na terapêutica da insuficiência cardíaca / Use of the beta-blockers in the heart failure treatment

Considerando o crescente interesse e o constante aporte de novas informaçoes sobre o uso de betabloqueadores no tratamento da insuficiência cardíaca, os autores fazem uma ampla revisao do assunto. Nessa abordagem, sao focalizados os dados mais recentes de interesse prático, aspectos controversos e detalhes conclusivos

Effects of the 5-HT receptor antagonists cyanopindolol, ICI 169,369, cisapride and granisetron on neuroleptic-induced catalepsy in mice

Typical neuroleptics (e.g. haloperidol) can induce catalepsy in rodents. Selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonists reduce neuroleptic-induced catalepsy (NIC), suggesting that this subtype of serotonin receptor plays a role in the modulation of nigrostriatal dopaminergic transmission. The present study was designed to evaluate the participation of other 5-HT receptor subtypes in NIC. Adult albino mice (both sexes, 26-35 g) were used. Catalepsy was induced with haloperidol (H; 1.5 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Cyanopindolol (a 5-HT1B receptor antagonist), ICI 169,369 (a 5-HT1C/2 receptor antagonist) and granisetron (a 5-HT3 receptor antagonist) were used. Buspirone, a 5-HT1A partial antagonist, cisapride, a 5-HT3/5-HT4 ligand and clomipramine, a 5-HT neuronal uptake blocker, were also employed. These drugs were injected ip, 20 min before H, with each animal (9-10 per group) used only once. Cyanopindolol (0.3 mg/kg) or ICI 169,369 (5 mg/kg) did not significantly affect NIC (375 +/- 39 and 378 +/- 34 s vs 372 +/- 44 s for controls, at 2 h after H). Buspirone (1 mg/kg) reduced, while pretreatments with either granisetron (0.5 mg/kg), cisapride (5 mg/kg) or clomipramine (5 mg/kg) potentiated the cataleptic effect of H (107 +/- 19, 576 +/- 52, 815 +/- 76 and 800 +/- 97 s vs 374 +/- 40 s in the control group, at 2 h after H).(ABSTRACT TRUNCATED AT 250 WORDS)

Teste da estimulacao sonica em gestantes hipertensas sob tratamento com beta-bloqueador (Pindolol) / Sound stimulation test during treatment of maternal hypertension with beta-adrenoceptor blockers (Pindolol)

Estudo do Teste da Estimulacao Sonica (TES) efetuado em 46 gestantes tratadas com Pindolol e Levomepromazina (9 mg/dia) divididas em tres grupos, I, II e III, respectivamente com 10, 20 e 30 mg/dia de Pindolol. Todas foram submetidas a operacao cesariana antes do inicio das contracoes do trabalho de parto. Para a analise da resposta cardiaca fetal foram consideradas a amplitude e a duracao da cardioaceleracao. Houve diminuicao da resposta cardiaca verificada por estas duas variaveis com o incremento do beta-bloqueador, sem contudo, haver significado estatistico. Todavia, a resposta cardiaca nos tres grupos foi significamente menor quando comparada com a resposta verificada por Zugaib e "col. POT. 19" em 30 gestantes hipertensas tratadas apenas com 9 mg/dia de Levomepromazina.

Estudo comparativo dos efeitos hemodinâmicos agudos do pindolol e do propanolol em pacientes portadores de cardiopatia isquêmica / Compartive study of the acute hemodynamic effects of pindolol and propranolol in patients with ischemic heart disease

Os efeitos agudos do Propranolol usado na dose de 3mg em 22 pacientes, e do Pindolol, na dose de 0,5mg em 24 pacientes foram estudados em situaçäo basal e 5 minutos após sua administraçäo. A análise comparativa das variáveis demonstrou näo ter havido diferença significativa no efeito de ambas as drogas sobre a pressäo máxima e a pressäo diastólica final de ventrículo esquerdo, as pressöes máxima, mínima e média de aorta, sobre o índice sistólico, e diastólico finais de ventrículo esquerdo, dp/dt máxima e mínima de ventrículo esquerdo e resistência vascular sistêmica (P > 0,05). O Propranolol elevou a pressäo diastólica final de ventrículo direito, reduziu o índice e a freqüência cardíaca, a fraçäo de ejeçäo e a velocidade de encurtamento circunferencial do ventrículo esquerdo (P < 0,05), alteraçöes näo observadas após o Pindolol. O Pindolol determinou elevaçöes significativas nas pressöes máximas de ventrículo direito, máxima, mínima e média de artéria pulmonar (P < 0,05), alteraçöes näo observadas após o Propranolol. A presssäo média do átrio direito aumentou significativamente após uso dos dois medicamentos (P < 0,05). As propriedades simpaticomiméticas do pindolol foram identificadas no presente trabalho, pela tendência que este demonstrou para aumentar o débito cardíaco, reduzir a resistência periférica e melhorar a motilidade segmentar do miocárdio isquêmico

Inhibition of chlorpromazine-induced catalepsy by the 5-HT-1A ligands pindolol and Buspirone in mice

Neuroleptcs such as chlorpromazine and haloperidol are capable of inducing catalepsy in rodents. Non-selective 5-hydroxytryptamine (5-HT) antagonists such as methysergide reduce the cataleptic effect of haloperidol. The present study was designed to evaluate the particpation of 5-HT-1A receptors in chlorpromazine-induced catalepsy in mice. Pundolol and buspirone, two putative 5-HT-1A receptor ligands, were used. Pretreatment with these drugs reduced the cataleptic effect of chlorpromazine. Clomipramine, a 5-HT neuronal uptake blocker, reversed the inhibitory effect of buspirone. Pretreatment with clomipramine alone caused a potentiation of neuroleptic-induced catalepsy. These results suggest that central 5-HT-1A receptors play an important role in neuroleptic-induced catalepsy in mice

Influência de betabloqueadores com atividade simpaticomimética intrínseca sobre pressäo arterial e lípides sanguíneos em portadores de hipertensäo arterial essencial / Effect of beta blockers with intrinsic sympathomimetic activity on blood pressure and blood lipids in patients with essential hypertension

Com a finalidade do comparar os efeitos de um betabloqueador com atividade simpaticomimética intrínseca (ASI) aos de um sem ASI, foram selecionados hipertensos com idade superior a 50 anos estudados durante quatro semanas e compreendendo três grupos: A) mepindolol (com ASI) 5mg/dia, 10 pacientes; B) metoprolol "duriles" (sem ASI) 200 mg/dia, 9 pacientes; C) placebo, 10 pacientes. Realizaram-se avaliaçäo clínica, prova ergométrica e dosagem de lípides sangüíneos antes e após o tratamento. O estudo da influência das drogas foi realizado pela análise de perfil. Em repouso, as três substâncias administradas reduziram igualmente a pressäo sistólica (PS), pressäo diastólica (PD) e freqüência cardíaca (FC). As médias de PS, PD e FC, em repouso, pós-tratamento foram respectivamente: 154,0, 95,5, 73,7 (grupo A); 148,8, 94,4, 70,1 (grupo B); 153,0, 96,0, 77,8 (grupo C). Na prova ergométrica houve reduçäo da PS, FC e duplo produto (DP) nos três grupos. A PD näo sofreu influência das drogas. As médias de PS, PD, FC e DP na carga máxima comum para os três grupos, na fase pós-tratamento, foram respectivamente: 198,0, 115,5, 124,3, 246,9 (grupo A); 198,8, 114,4, 144,6, 283,2 (grupo B); 202,2, 119,0, 143,5, 283,4 (grupo C). Em relaçäo ao perfil lipídico houve apenas uma discreta elevaçäo dos níveis séricos de triglicérides e de VLDL-colesterol após o tratamento. Em concluäo, o emprego do mepindolol e do metroprolol "duriles" foi igualmente útil na reduçäo dos níveis de pressäo arterial de hipertensos...

Funçäo ventricular no prolapso de valva mitral: efeitos do bloqueio beta-adrenérgico com e sem atividade simpatomimética intrínseca / Ventricular function in mitral valve prolapse: effects of beta adrenergic blockers with and without intrisic sympathomimetic activity

Admite-se, de acordo com a teoria cardiomiopática da etiopatogenia do prolapso valvar mitral, que pode existir grau discreto de comprometimento miocárdico näo evidenciável em condiçäo basal, mas passível de ser desmascarado sob efeito de fatores depressores associados. Como os bloqueadores beta-adrenérgicos constituem opçäo primeira no controle sintomático desses pacientes, testou-se a hipótese de que o seu efeito depressor pudesse ser evidenciado em pacientes com prolapso valvar mitral. Os resultados deste estudo, utilizando avaliaçäo da funçäo ventricular por métodos ecocardiográfico e angiocardiográfico nuclear, näo säo indicativos da presença de processo cardiomiopático em tais pacientes. Entretanto, foi possível verificar, ainda que dentro dos limites da normalidade para desempenho ventricular, reduçäo da fraçäo de ejeçäo, da freqüência cardíaca e da velocidade máxima de esvaziamento ventricular, sob açäo de bloqueador sem atividade simpatomimética intrínseca (propranolol), mas näo de bloqueador provido de atividade simpatomimética intrínseca (pindolol)

Improvement in wall motion after pindolol: a mechanism for the preservation of left ventricular function in coronary artery disease

In order to evaluate the mechanism by which beta blockers with intrinsic sympathomimetic activity preserve left ventricular systolic function at rest, 46 patients with coronary artery disease were studied by right and left heart catheterization and left ventriculography. Patients were studied using a double-blind, randomized protocol before and after a single intravenous dose of 3 mg propanolol (N = 22) or 0.5 mg pindolol (N = 24). Mean right atrial pressure increased similarly after both drugs. Mean pulmonary artery pressure, left ventricular end-diastolic pressure, mean aortic pressure, and peripheral vascular resistance did not change significantly after either drug. Cardiac index (before: 3.0 + or - 0.7(mean + or - SEM); after: 2.8 + or - 0.2 1 min **-1 m**-2) and heart rate (before: 78 + or - 15; after: 72 + or - 12 bpm) deveased only after propranolol administration. Ejection fraction decreased only after propranolol (48 + or - 16 to 41 + or - 15%). Improvement in segmental wall motion abnormalities was noted (23 of 47 segments) only after pindolo. The total left ventricular wall motion score improved after pindolol and worsened after propranolol (P<0.5). In patients with impaired left ventricular function, pindolol administration resulted in improved resting ejection fraction. Thus, the acute hemodynamic consequences of pindolol administration differ from those of propranolol owing to the preservation of left ventricular systolic function which seem to be related to the...

Estudo comparativo com pindolol e metildopa em gestantes com hipertensäo arterial crônica / Comparative study with pindolol and methyldopa in pregnant women with chronic hypertension

Foram tratadas 40 gestantes com hipertensäo arterial crônica, 20 consecutivas com a metildopa e 20 com pindolol. A dose inicial da metildopa foi de 250 mg duas vezes ao dia, até o máximo de 2.000 mg. Principiou-se com o pindolol, na dose de 10 mg, até o máximo de 30 mg. Prescreveram-se hipotensores a partir de uma pressäo arterial diastólica de 95 mmHg. No grupo do pindolol houve diminuiçäo significativa da pressäo arterial, pelo teste t de Student para grupos pareados, p<0,01 (pressäo arterial média pré-tratamento 153,25 + ou - 6,34 x 104,25 + ou - 4,94 mmHg e pressäo arterial média pós-tratamento 143,75 + ou - 9,44 x 93,25 + ou - 9,63 mmHg). A necessidade de associaçäo com outros fármacos (nifedipina e hidralazina) foi significativamente menor no grupo do pindolol, 4/20, de que no grupo da metildopa, 9/20, p<0,05, pelo teste do X2. O aparecimento de pré-eclâmpsia superposta e os resultados neonatais (peso, índice de Apgar e neomortos) näo apresentaram diferenças estatisticamente significativas nos dois grupos, p>0,05, pelos testes t para grupos independentes, do X2 e exato de Fischer

Interaction between pindolol and malothan anaesthesia in dogs: effects on blood sugar and serum potassium levels and liver tissue

The aim from the present work was to study the effect of the interaction between pindolol and halothane anesthesia on the fasting blood sugar and serum potassium levels and liver tissue in dogs. Six male mongrel dogs were anesthetized with thiopentone sodium, followed by endotracheal intubation and controlled ventilation. Halothane 1% in oxygen was used for maintenance. Twenty minutes after halothane administration, 1 mg of pindolol was injected via a femoral vein. Venous blood samples were taken before halothane, 10 and 20 minutes after halothane and 10 and 20 minutes after pindolol. They were analyzed for blood sugar and serum potassium levels. A piece of liver tissue was excised [control] immediately after halothane administration and 20 minutes after pindolol injection. Results showed significant decrease in blood sugar levels 10 and 20 minutes after pindolol. No significant changes occurred in serum potassium and no pathognomonic changes were found in liver tissue. It is concluded that hypoglycemia may be a possible risk if pindolol is injected during halothane-oxygen anesthesia

Efecto de la combinación pindolol-clopamida en el tratamiento de la hipertensión leve y moderada: un estudio multicéntrico / Effect of combined pindolol-clopamide in essential and moderate hypertension therapy: a multicentric study

En el presente estudio se reporta el efecto antihipertensivo de la combinación Pindolol + Clopamida vs placebo, en grupos paralelos, con distribución al azar, en un grupo de pacientes hipertensos leves y moderados que asistieron a los Servicios de Medicina Vial del Estado Carabobo. El estudio duró ocho semanas, con exámenes clínicos cada dos semanas. La dosis de Pindolol + Clopamida fue de 1 tableta (10 mg y 5 mg respectivamente). El grupo de pacientes seleccionados perteneció mayormente al sexo masculino (19 pacientes de 20 pacientes en las edades de 30 y 49 años en el grupo placebo; y 16 pacientes de 20 pacientes en las edades de 30 y 49 años en el grupo Pindolol + Clopamida). En el grupo que recibió el tratamiento activo, en el 60% de los pacientes los valores tensionales se normalizaron al final del tratamiento y en el 40% hubo reducciones apreciables, pero no alcanzaron la normalidad. En el grupo placebo apenas hubo descenso a la normalidad en el 20% de los pacientes. Nosotros concluimos que la combinación Pindolol + Clopamida es util en la terapia de la Hipertensión leve y moderada y exhibe excelente tolerancia

Enflurane Anesthesia for Surgical Removal of Pheochromocytoma / 대한마취과학회지

A 66 year old male with a suprarenal pheochromocytoma on the left side was treated preoperatively with oral phenoxybenzamine 20 mg, b. i. d. for 2 weeks. The night before surgery, phenobarbital 100 mg & diazepam 5 mg were given orally. One hour before induction, diazepam 10 mg i. m. was given. Preinduction BP was 210/140 and HR was 130/min. After diazepam 20 mg i. v, BP lowered to 200/130 and HR lowered to 126/min. With commencement of sodium nitroprusside i. v. dripping, a BP of 160/100 and HR of 118 were maintained. Following Thiopental sodium 250 mg i. v., mask induction was started with N2O-O2-Enflurane and pancuronium 4 mg i. v., after 5 minutes, a #8.5 tube was intubated and pindolol 0.16 mg was injected to prevent tachycardia. We maintained a tolerable BP and pulse by repeatedly adding a bolus i. v. injection of phenoxybenzamine 1 to 2 mg during tumor manipulation and removal. No arrhythmia was noted throughout the procedure, except tachycardia. After removal of the tumor, with rapid blood transfusion and fluid infusion plus dopamine i. v. dripping, a tolerable BP and pulse was maintained.