The antihypertensive effect and side reaction of pindolol were studied in 48 cases of essential hypertension 5mg to 15mg once regiment for average period of 6 weeks. 1) Average reduction of 25.11mmHg in systolic and 16.36mmHg in diastolic pressure were observed and their percentile reduction was 15.20% and 14.79%, respectively. The overall effect rate was 83.21%. The blood pressure was lowered significantly since 1 week of both in systolic and diastolic pressure with the daily of 10-15mg. 2) There was no significant change in heart rate before and after treatment. 3) No specific side reaction was observed except 1 cases in which discontinued the medication because of severe headache and fatigability on 2nd day of medication.
Blood Pressure ; Headache ; Heart Rate ; Hypertension ; Pindolol

To estimate the clinical efficacy of a newly developed beta1 and beta2 - adrenoreceptor antagonist, levobunolol hydrochloride (Betagan), fifty six patients (96 eyes) with various types of glaucoma were enrolled in this study and were treated twice a day with 0.5% Betagan. Intraocular pressure (lOP), visual acuity, pupil size and cup/disc ratio were measured before and after Betagan treatment, at week 1, 2, 4, 8 and 12. The patients were also examined to check the subjective or objective local adverse reactions. All the patients showed significant reduction of lOP throughout the observation period without significant change of visual acuity, pupil size and cup/disc ratio. Additive hypotensive effect of Betagan was also noted when it was added to pilocarpine. In some patients, however, stinging sensation with tearing, photophobia, or foreign body sensation and punctate corneal erosion were noted after Betagan treatment; those were mild and transient.
Bites and Stings ; Foreign Bodies ; Glaucoma ; Humans ; Intraocular Pressure ; Levobunolol* ; Photophobia ; Pilocarpine ; Pupil ; Sensation ; Tears ; Visual Acuity

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.
Aged ; Anesthesia* ; Arrhythmias, Cardiac ; Blood Transfusion ; Diazepam ; Dopamine ; Enflurane* ; Humans ; Male ; Masks ; Nitroprusside ; Pancuronium ; Phenobarbital ; Phenoxybenzamine ; Pheochromocytoma* ; Pindolol ; Tachycardia ; Thiopental

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.
Alprazolam ; Citalopram ; Clonazepam ; Humans ; Panic Disorder ; Panic ; Paroxetine ; Pindolol ; Prospective Studies ; Quetiapine Fumarate ; Transcranial Magnetic Stimulation ; Tranylcypromine

The diurnal variation of introcular pressure was measured in 40 eyes of 20 healthy Koreans and in 50 eyes of 25 patients with chronic open angle glaucoma and ocular hypertension with and without levobunolol and dipivefrine. The intraocular pressure was measured every 1 hour from 8:00 o'clock by the same examiner using with Goldmann applanation tonometry. The levobunolol, a new beta-adrenoceptor antagonist effective in the long-term treatment of glaucoma and the dipivefrine, a prodrug of epinephrine which is alpha-and beta-adrenergic agonist, both decrease intraocular pressure despite of opposite pharmacologic actions. Several clinical studies have demonstrated additional effect when an epinephrine compound is added to timolol, a beta-blocker antagonist, theraphy. It is the most important issue that determination of the time of instillatiolt related to the time of maximum effec: of the drugs and the time of the highest intraocular pressure in a day in every each patient. The authors obtained the following results; 1) In the control group, the mean intraocular pressure was 15.3 +/- 1.377 mmHg, the highest was 17.3 +/- 0.924 mmHg at 10 o'clock AM and the lowest was 13.7 +/- 1.764 mmHg at 3 o'clock PM. The diurnal variation was 3.60 +/- 1.743 mmHg.(p=0.002). 2) In the patient group, the mean intracular pressure was 28.5 +/- 1.606 mmHg, the highest was 31.4 +/- 2.986 mmHg at 10 o'clock AM and the lowest was 26.1 +/- 0.836 mmHg at 4 o'clock PM. The diurnal variation was 5.31 +/- 1.101 mmHg.(p=0.0001). 2) The lowering effect of intraocular pressure by the instillation of 0.5% levabunolol and 0.1% dipivefrine was statistically significant(p=0.0001) both in the control group and patient group. In the patient group, the maximum effect was made at 5 hours after instillation of the drugs with 28% decrease. 4) The distribution of the highest intraocular pressure in the patient group was as following: 23 eyes at 10 o'clock AM, 11 eyes at 9 AM, 9 eyes at 11 AM, 3 eyes at 8 AM, 3 eyes at noon and 1 eye at 4 o'clock PM.
Adrenergic beta-Agonists ; Epinephrine ; Glaucoma ; Glaucoma, Open-Angle* ; Humans ; Intraocular Pressure ; Levobunolol* ; Manometry ; Ocular Hypertension ; Pharmacologic Actions ; Timolol

The only clinically avilable levo-isomer type of beta-recepter blocker is penbutolol sulfate, and it is already accepted as one of beta-receptor blockers for initial antihypertensive drug therapy according to the report of 1988 Joint National Committee on Detection, Evaluation, and Tratment of High Blood Pressure. To evaluate the antihypertensive efficacy, effect on the quqlity of life, and side effects of penbutolol recently introduced into Korea, penbutolol was administered to 29 essential hypertensive(mild 9, moderate10, and severe 10) patients for 12 weeks or longer. The result of the clinical analysis are as follows; 1) The mean age was 50.0+/-10.9(M+/-SD), and the sex distribution between male and female was16:13. 2) The blood pressure lowering effects of penbutolol as a monotherapy were marked in 16, moderate in 6, and insignificant in 2 cases. The systolic blood pressure was significantly decreased from 179.1+/-20.2 to 135.4+/-16.5mmHg(P<0.005), and the diastolic blood pressure from 112.6+/-13.5 to 84.0+/-11.9mmHg(P<0.005)after 12 weeks' penbutolol therapy. 3) The heart rate was significantly decreased from70.3+/-13.3 to 65.5+/-9.1 per minute(P<0.05). 4) The quality of life was improved markely in 5(17.2%) and slightly in 8 cases(29.6%). 5) There were no significant laboratory changes after 12 weeks' penbutolol therapy. 6) Two out of three cases with non-specific ST segment and T wave changes in EKG and two out of 9 cases with EKG were normalized, 2 cases of LAH with strain were improved. 7) The side effects of penbutolol were dizziness in 4, sexual dysfunction in 2, and skin rash in 1 case. 8) Final multifarious assessment of penbutolol therapy showed that it was very useful in 11(37.9%), useful in 4(13.8%) and slightly useful in 7 cases(24.1%). These reult suggest that penbutolol is a first-line antihypertensive agent with an effective antihypertensive action, improving quality of life, with no significant laboratory changes and few side effects.
Blood Pressure ; Dizziness ; Drug Therapy ; Electrocardiography ; Exanthema ; Female ; Heart Rate ; Humans ; Hypertension ; Joints ; Korea ; Male ; Penbutolol ; Pheniramine ; Quality of Life ; Sex Distribution

OBJECTIVETo study the correlation between the absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments and their molecular structural parameters.

METHODSThe net atomic charges and the molecular volumes of 11 beta-adrenoreceptor antagonists were obtained with the semiempirical self-consistent field molecular orbital calculation CNDO/2 method and Mont Carlo method respectively, using the minimum energy conformation obtained from the optimization of the standard molecular geometry with the molecular mechanics MM+ method. The stepwise multiple regression analysis was used to obtain the correlation equations.

RESULTSThe absorption rate constants of beta-adrenoreceptor antagonists in rat jejunum or ileum were well linearly correlated with the sum of the net charges of all hydrogen atoms and the molecular volumes. The beta-adrenoreceptor antagonist with higher lipophilicity, weaker hydrogen-bonding potential,and smaller molecular volume had greater absorption rate constants.

CONCLUSIONThe absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments are mainly related with their lipophilicity,hydrogen-bonding potential and molecular size.

Adrenergic beta-Antagonists ; chemistry ; pharmacokinetics ; Animals ; Intestinal Absorption ; Intestine, Small ; metabolism ; Metoprolol ; pharmacokinetics ; Molecular Structure ; Nadolol ; pharmacokinetics ; Propranolol ; pharmacokinetics ; Rats ; Regression Analysis

Color Doppler imaging (CDI) was carried out to evaluate the effects of anti-glaucoma drugs on ophthalmic circulation using CDI-derived resistive index (RI) values. CDI was performed on nine Beagle dogs, and RI values were calculated for the medial long posterior ciliary artery before and after the administration of anti-glaucoma drugs. A significant increase in RI values was found after topical administration of levobunolol (p < 0.05) or dipivefrin (p < 0.05). Pilocarpine showed no effects on RI values after topical administration. The results suggest that some anti-glaucoma drugs could affect ophthalmic blood flow.
Adrenergic Agonists/pharmacology ; Animals ; Ciliary Arteries/*drug effects/*ultra ; Dogs ; Epinephrine/analogs & derivatives/therapeutic use ; Eye/*blood supply ; Female ; Glaucoma/*drug therapy ; Levobunolol/therapeutic use ; Male ; Ocular Physiological Phenomena ; Pilocarpine/therapeutic use ; Ultra ; *Vascular Resistance

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.
Animals ; Benzothiazoles ; pharmacology ; Brain Chemistry ; drug effects ; Epilepsy ; chemically induced ; complications ; Hippocampus ; chemistry ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Histidine ; pharmacology ; Hypothalamus ; chemistry ; Kindling, Neurologic ; physiology ; Memory Disorders ; drug therapy ; etiology ; Pentylenetetrazole ; Phenoxypropanolamines ; pharmacology ; Piperidines ; pharmacology ; Pyrilamine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H2 ; drug effects ; physiology ; Spatial Memory ; drug effects ; Spectrometry, Fluorescence ; Thalamus ; chemistry

The study is to observe the effect of racemic TJ0711 on blood pressure and heart rate as well as protection of cardiovascular system of renal hypertensive rats after long-term administration. The renal hypertensive models were established by the two-kidney, one-clip (2K1C) method in Wistar rats. Four weeks later, assigned the rats whose SBP had increased at least 4 kPa randomly into 5 groups: racemic TJ0711 10, 20 and 40 mg x kg(-1) groups, carvedilol control group, model group and sham group (n=10), ig administration once daily. The changes of BP (blood press) and HR (heart rate) before and after administration were measured by tail-cuff method weekly. Plasma samples of all animals were taken in 6-8 weeks, and plasma MDA as well as renin, angiotensin II (Ang II) and endothelin-1 (ET-1) levels were measured. Left ventricle was cut off after 9 weeks, and left ventricular weight index (LVWI) and hydroxyproline were measured. The significant decrease of the BP of TJ0711 40 mg x kg(-1) group was observed after TJ0711 ig administration for 4 weeks, and this effect remained till the end of the study. In 8th week, the systolic blood pressure values were: TJ0711 40 mg x kg(-1) group 18.93 +/- 1.82 kPa (vs 21.30 +/- 2.30 kPa, P < 0.05); 20 mg x kg(-1) group 20.68 +/- 3.29 kPa (vs 22.19 +/- 2.88 kPa). The plasma MDA level of all treated groups was significantly lower than that of model group, so were the plasma renin, Ang II and ET-1 levels (P < 0.05). LVWI and hydroxyproline content of myocardial tissue decreased to some extent, but was not significant as compared with that of model group. The study showed that TJ0711 repeated dosing could reduce BP level beginning from drug administration; besides block adrenal alpha and beta receptors to play an antihypertensive role. The sustained antihypertensive effect also related to reduce plasma vasoconstrictor substances and oxidation product MDA. These effects benefited cardiovascular protection.
Angiotensin II ; blood ; Animals ; Antihypertensive Agents ; administration & dosage ; pharmacology ; Blood Pressure ; drug effects ; Endothelin-1 ; blood ; Female ; Heart Rate ; drug effects ; Heart Ventricles ; metabolism ; pathology ; Hydroxyproline ; metabolism ; Hypertension, Renal ; blood ; physiopathology ; Longitudinal Studies ; Male ; Malondialdehyde ; blood ; Organ Size ; drug effects ; Phenoxypropanolamines ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Renin ; blood