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PubMed1999

Transformed migraine is a cause of chronic daily headaches.

Chronic daily headaches (CDH) consist of episodes of head pain occurring daily; more than 15 days each month; often associated with a history of migraine, with or without aura; or with a history of tension-type headaches occurring alone or both occurring together. Chronic daily headaches are frequently associated with rebound headaches after ergotamine, barbiturate, caffeine, and analgesic abuse. We previously reported that migraineurs with typical intermittent headaches exhibited excessive cerebral cortical vasodilation after oral acetazolamide which usually precipitated and reproduced their typical headaches. In the present study, cerebral vasodilator responses were tested by measuring changes in local cerebral blood flow (Delta LCBF) utilizing xenon-contrasted CT scanning, before and after oral administration of 14.3 mg/kg of acetazolamide, in 11 patients with CDH. The results were compared with 12 age-matched typical migraineurs, with and without aura, who had a history of migraine attacks occurring at intervals of 1 month or longer. Global and subcortical gray and white matter Delta LCBFs were quantitated and compared between both groups. After acetazolamide, Delta LCBF increased in cortical gray matter by 11.8% among patients with CDH and by 16.7% among migraineurs, with no significant differences between groups. Typical migraine attacks were provoked by acetazolamide in 9 patients (82%) with CDH and in 11 (92%) migraineurs with intermittent headaches. These observations are taken as evidence that at least 82% of patients with CDH have transformed migraine as judged by the provocation by acetazolamide of typical migraine attacks associated with excessive Delta LCBF increases. Serotonin agonists should be considered in the treatment of CDH to avoid ergotamine, caffeine, barbiturate, and analgesic abuse.

Acetazolamide↗
PubMed1982

Effect of sulfonamides on the hypercalcemic response to vitamin D.

Parathyroidectomized rats were fasted for twenty-four hours then treated with 10(6) units/kg of vitamin D3. Twelve hours later the animals were bilaterally nephrectomized and treated with either the appropriate control solution or one of the following: acetazolamide, methazolamide, ethoxzolamide or CL 13,850. Animals treated with the vitamin exhibited an increase in plasma calcium of approximately 5 mg/dl. This response was antagonized by treatment with acetazolamide, methazolamide or ethoxzolamide. These agents are all sulfonamide inhibitors of carbonic anhydrase. CL 13,850, a structural analog of acetazolamide that is devoid of enzyme inhibitory activity, was also devoid of inhibitory activity with respect to the hypercalcemic response to vitamin D3. Acetazolamide inhibited the response to the vitamin at doses yielding ultrafiltrable plasma drug concentrations of approximately 10(-5) to 10(-4) M. The hypercalcemic response observed following the administration of the active metabolite of vitamin D3 (1,25-dihydroxyvitamin D3) was attenuated by treatment with acetazolamide.

Acetazolamide↗
PubMed2002

Regional cerebral blood flow measured by the resting and vascular reserve (RVR) method in chronic alcoholics.

It has been reported that cerebral blood flow is decreased in chronic alcoholics without neurological diseases. We performed SPECT by the resting and vascular reserve (RVR) method in 11 chronic alcoholics (mean age 59.1 +/- 10.4, all males) and 11 age-matched healthy controls (mean age 58.8 +/- 10.1, all males). The resting and vascular reserve (RVR) method is a consecutive (99m)Tc-ECD SPECT study before and after acetazolamide administration with adjunctive radionuclide angiography, which is easy to perform for a routine clinical study and quite useful for evaluating regional cerebral blood flow and the cerebrovascular response to acetazolamide. Regional cerebral blood flows in almost all regions in the alcoholic group were lower than those in the control group. However, there were no significant differences in increased rates of blood flow in response to acetazolamide in almost all regions between the chronic alcoholic group and the control group. In both groups, the increased rates of blood flow in response to acetazolamide in the supratentorial region, cerebellum, and brain stem were 30-40%, 20-25%, and 42-48%, respectively. The cerebrovascular response to acetazolamide in chronic alcoholics was not impaired, therefore the reduction of brain metabolism may be one of the important factors causing the decreased cerebral blood flow in chronic alcoholics.

Acetazolamide↗
PubMed1982

Abolished relationship between pancreatic HCO-3 secretion and arterial pH during carbonic anhydrase inhibition.

After acetazolamide administration, CO2 hydration in pancreatic cells would be slow and might become a rate-limiting factor to pancreatic HCO-3 secretion. Correspondingly, pancreatic HCO-3 secretion-normally pH dependent-would become slow and pH-independent. However, acetazolamide would not be expected to interfere with the capacity of the secretory mechanism to generate a proton potential gradient between pancreatic cells and interstitial fluid. These predictions were examined in 5 anesthetized, secretion infused (2.7 C. U./kg b.wt. h-1) pigs. Pancreatic juice was collected from a catheter in the pancreatic duct. Arterial pH was varied through i.v. HCl and NaHCO3 infusions and CO2 addition to inspired air. Before acetazolamide, HCO-3 secretion varied with plasma pH and averaged 298 +/- 30 mumol/min at control arterial pH. Acetazolamide (150 mg/kg, i.v.) reduced HCO3 secretion to 84 +/- 12 mumol/min and rendered secretion independent of arterial pH between pH 7.6 and pH 7.0. It is concluded that acetazolamide imposes a pH-independent transport maximum on pancreatic HCO-3 secretion, but does not reduce the capacity of the secretory mechanism to sustain a proton potential gradient between cells and interstitial fluid.

Acetazolamide↗
PubMed2003

Bicarbonate-dependent chloride secretion in Calu-3 epithelia in response to 7,8-benzoquinoline.

Stimulation of Calu-3 epithelia with 7,8-benzoquinoline, under short circuit current conditions, produced a current increase that was completely accounted for by the net flux of chloride, measured simultaneously with 36Cl-. Nevertheless the current stimulated by 7,8-benzoquinoline was sensitive to acetazolamide, which caused up to 50 % inhibition of the stimulated current, the remainder being sensitive to the Na+-K+-2Cl- cotransport inhibitor bumetanide. The effects of acetazolamide could be mimicked by either amiloride or by the di-sodium salt of 4,4'-dinitrostilbene-2,2'-disulphonic acid (DNDS) added to the basolateral side of the epithelium, but their actions were not additive. Amiloride was needed in sufficient concentration to inhibit the sodium-proton exchanger NHE1. DNDS blocks both the chloride-bicarbonate exchanger AE2 and the sodium-bicarbonate transporter NBC1. However, since 7,8-benzoquinoline activates basolateral K+ channels, causing hyperpolarisation, it is unlikely NBC1 is active after addition of 7,8-benzoquinoline. The effect of DNDS is, therefore, mainly on AE2. It is concluded that chloride enters the basolateral aspect of the cells using the Na+-K+-2Cl- cotransporter and a parallel arrangement of NHE1 with AE2, these latter two being sensitive to acetazolamide because of their association with the cytoplasmic form of carbonic anhydrase CAII. The effects of acetazolamide could be mimicked by removal of HCO3-/CO2 from the bathing medium, and furthermore showed that the NHE1-AE2 mechanism is particularly important when the transport rate is high. Thus part of the current stimulated by 7,8-benzoquinoline and inhibited by acetazolamide or HCO3-/CO2 removal can be said to represent bicarbonate-dependent chloride secretion.

Acetazolamide↗
PubMed1977

Use of inhibitors in physiological studies of carbonic anhydrase.

The appropriate use of acetazolamide in examining physiological function is based on the following: 1) the dissociation constant of the drug-carbonic anhydrase complex (10(-8) M); 2) the concentration needed to eliminate the catalyzed reaction (10(-4) M can be achieved readily in tissues by giving 20 mg/kg at no toxicity; and 4) the lack of known effects on any other systems at concentrations below 10(-3) M. Several problems have been identified and are analyzed concerning the use of acetazolamide and allied drugs. Concentrations greater than 10(-3) M have been used in vitro and occasionally in vivo, generating nonspecific effects. Experiments in which the substrate (CO2) is varied over a large range have been interpreted without regard to alteration in both the catalyzed and uncatalyzed rates, leading to conclusions that acetazolamide acts on a transport system other than carbonic anhydrase, while in reality the drug is acting on carbonic anhydrase at different levels of its catalytic rate. Since calculation of the uncatalyzed hydration of CO2 or dehydration of HCO3-in tissues involves some uncertainty, these rates are generally best defined by studying the dose-response curves of inhibitors and observing the residual activity after full inhibition. The kidney is an exception, since here the residual rate also involves an entirely separate process. Inhibitors other than acetazolamide are useful in ruling out nonspecific effects, and in gaining certainty of access to cells. Compounds closely akin to the inhibitors, but lacking action upon carbonic anhydrase, are also available as controls. It is emphasized that acetazolamide and other carbonic anhydrase inhibitors, when properly used, are highly specific probes of a single enzyme that has a wide variety of physiological functions.

Acetazolamide↗
PubMed1992

A comparison of transcranial Doppler and cerebral blood flow studies to assess cerebral vasoreactivity.

BACKGROUND AND PURPOSE: The aim of this study was to determine the ability of transcranial Doppler ultrasonography when used to assess cerebral vasoreactivity. The results of this method were compared with regional cerebral blood flow measurements. METHODS: Forty-three patients with symptoms suggesting cerebrovascular disease took part. Transcranial Doppler findings in the middle cerebral arteries were compared with regional cerebral blood flow in the corresponding perfusion territories before and after acetazolamide administration. RESULTS: There was a significant positive correlation between the absolute increase in cerebral blood flow in milliliters per 100 g per minute and the percent increase in velocity (r = 0.63). The right-left, side-to-side difference of the acetazolamide response obtained by the two methods also showed a positive correlation (r = 0.80). Control limits obtained from healthy subjects were used for both the blood flow increase (absolute values and asymmetry in absolute values) and the velocity increase (percent increase and asymmetry in percent increase). The two methods then agreed in their evaluation of vasoreactivity in 74 (86%) of the 86 middle cerebral artery perfusion territories; 20 (23%) were assessed by both methods as having a reduced vasodilatory reserve. Eleven hemispheres with a slightly reduced regional cerebral blood flow response to acetazolamide were not detected by transcranial Doppler, whereas all territories with a marked reduction were identified by Doppler. Only one hemisphere with a normal cerebral blood flow increase after acetazolamide administration was assessed by Doppler as having reduced vasoreactivity. CONCLUSIONS: Transcranial Doppler and the acetazolamide test may be used in clinical situations to assess cerebral vasoreactivity.

Acetazolamide↗
PubMed1973

Sodium-independent active potassium reabsorption in proximal tubule of the dog.

Prior studies of proximal tubule reabsorption have failed to distinguish conclusively between a separate active K+ transport system and K+ movement linked to Na+ reabsorption. To attempt to dissociate movement of K+ from Na+ and Ca++, recollection micropuncture experiments were performed in proximal tubules of intact and thyroparathyroidectomized (TPTX) dogs under two different conditions known to inhibit Na+ reabsorption: saline expansion to 5% body wt, and 5 mg/kg acetazolamide. A control hydropenic group was also studied. Tubular concentrations of K+, Na+, and Ca++ were measured by electron probe analysis. During initial collections, mean+/-SEM tubular fluid/plasma (TF/P)(K+) was 1.07 +/-0.05, 1.05+/-0.05, and 1.00+/-0.03 in intact hydropenic (n = 7), saline (n = 6), and acetazolamide (n = 8) groups; fractional reabsorption (FR) of K+ in proximal tubules was 0.35, 0.39, and 0.31 respectively. After saline, (TF/P)(Inul in) fell from 1.81 to 1.34 (P < 0.01); (TF/P)(K+), (TF/P)(Na+), and tubular fluid/ultrafiltrate, (TF/UF)(Ca++) did not change, so that FR of all three ions fell proportionately. After acetazolamide, however, despite a 24% inhibition of FR of Na+ and Ca++, (TF/P)(K+) fell to 0.85+/-0.04 (P < 0.005) so that FR of K+ was unchanged at 0.34. In three corresponding groups of TPTX dogs, similar results were obtained. Acetazolamide (n = 7) inhibited FR of Na+ and Ca++ by 41%, but (TF/P)(K+) fell from 1.03+/-0.03 to 0.89+/-0.04 (P < 0.005) so that FR of K+ was unchanged (0.36-0.34).A separate uphill transport system for K+ in proximal tubules is therefore unmasked by acetazolamide, a drug which selectively inhibits Na+ (and Ca++) reabsorption. Saline, on the other hand, inhibits net reabsorption of all three ions, probably by increasing passive backflux via intercellular channels.

Acetazolamide↗
PubMed1977

Mechanism of resistance to the phosphaturic effect of the parathyroid hormone in the hamster.

The effect of parathyroid hormone and calcitonin on the renal excretion of phosphate, calcium, and cyclic AMP was evaluated in the thyroparathyroidectomized hamster, a mammal apparently reisstant to the phosphaturic effect of parathyroid hormone. Parathyroid hormone did not increase phosphate excretion, although it decreased excretion of calcium and increased urinary excretion of cyclic AMP. This lack of a phosphaturic response to parathyroid hormone was not reversed by administration of 25-OH vitamin D or infusions of calcium or phosphate. Calcitonin, another potentially phosphaturic hormone, also vailed to increase phosphate excretion but markedly elevated urinary excretion of cyclic AMP. In hamsters pretreated with infusion of urinary ammonium chloride, which decreased plasma and urinary pH, both parathyroid hormone and calcitonin increased excretion of phosphate as well as that of cyclic AMP. Acetazolamide had no phosphaturic effect in ammonium chloride-loaded hamsters, and it decreased cyclic AMP and calcium excretion. Alkalinization of urine by acetazolamide did not prevent the phosphaturic effect of parathyroid hormone in ammonium chloride-loaded hamsters, but it blocked the increase in urinary cyclic AMP excretion. Parathyroid hormone and calcitonin both stimulated adenylate cyclase in a cell-free system (600-g pellet) from hamster renal cortex, elevated tissue cyclic AMP levels, and activated protein kinase in tissue slices from hamster renal cortex. In acid medium, the increase in cyclic AMP and activation of protein kinase in response to parathyroid hormone was diminished, but addition of acetazolamide restored responsiveness of both parameters to control values. Acetazolamide, on the other hand, did not influence adenylate cyclase or its response to parathyroid hormone or cyclic AMP phosphodiesterase activity. We conclude that the lack of a phosphaturic effect of parathyroid hormone and calcitonin in the hamster depends on steps in the cellular action of these hormones, steps that are sensitive to pH subsequent to cyclic AMP generation and protein kinase activation. In addition, acetazolamide may potentiate the phosphaturic effect of parathyroid hormone by promoting accumulation of cyclic AMP in tissue. Thus, the hamster is a particularly useful model for studies of syndromes in which there is renal resistance to phosphaturic hormones.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Transcranial Doppler assessment of cerebral perfusion reserve in patients with carotid occlusive disease and no evidence of cerebral infarction.

Using transcranial Doppler ultrasound (TCD), we measured bilateral middle cerebral artery mean blood flow velocities (MCAVs) before and 10 minutes after intravenous infusion of 1 gram of acetazolamide in 20 patients without cerebral infarction. Seven patients had normal carotid arteries (group 1), seven had unilateral internal carotid artery (ICA) stenosis > or = 75% (group 2), and six had unilateral ICA occlusion (group 3). Before acetazolamide infusion, side-to-side differences in MCAV were 0.06 cm/sec in group 1 (p = 0.98), 4.3 cm/sec in group 2 (p = 0.36), and 15.0 cm/sec in group 3 (p = 0.02). Bilateral MCAV increased in all three groups after acetazolamide infusion, and the side-to-side differences in MCAV were 3.2 cm/sec in group 1 (p = 0.40), 11.4 cm/sec in group 2 (p = 0.04), and 27.6 cm/sec in group 3 (p = 0.03). Patients with carotid stenosis or occlusion and ipsilateral transient ischemic attacks (TIAs) had higher side-to-side differences in MCAV before (p = 0.03) and after (p = 0.01) acetazolamide than did asymptomatic patients with carotid disease. The association of impaired cerebral perfusion reserve and TIAs suggests that the TCD-acetazolamide test may enable identification of a subgroup of patients with carotid occlusive disease who are at higher risk for stroke.

Acetazolamide↗
PubMed2004

Medroxyprogesterone at high altitude. The effects on blood gases, cerebral regional oxygenation, and acute mountain sickness.

OBJECTIVE: To study the effect of medroxyprogesterone on blood gases and cerebral regional oxygenation at high altitude, alone and in conjunction with acetazolamide, and to assess the effect on acute mountain sickness (AMS). DESIGN: Two placebo-controlled trials during rapid ascent to high altitude. PARTICIPANTS: In the first trial, 20 participants, and in the second trial, 24 participants. SETTING: During rapid ascent to 4680 m and on rapid ascent to 5200 m. INTERVENTION: In the first trial, participants were randomized to receive medroxyprogesterone 30 mg or a placebo twice a day. In the second trial, participants were randomly assigned to one of 4 groups: a placebo twice daily, medroxyprogesterone 30 mg twice daily, acetazolamide 250 mg plus a placebo twice daily, or acetazolamide 250 mg plus medroxyprogesterone 30 mg twice daily. MAIN OUTCOME MEASURES: Blood gas changes and symptom scores of AMS in both trials and cerebral regional oxygen saturations in the first trial only. RESULTS: Medroxyprogesterone improved peripheral oxygen saturations in both trials and improved PaO2 in combination with acetazolamide. Cerebral regional oxygen saturation was not altered by medroxyprogesterone. The reduction in symptom scores and in the extent of AMS was not significant in this limited study. CONCLUSIONS: Medroxyprogesterone acts as a respiratory stimulant, but the clinical benefit regarding the development of AMS was unproven at high altitude. Combined medroxyprogesterone and acetazolamide gave the best PaO2.

Acetazolamide↗
PubMed1997

Importance of cerebral blood flow to the recognition of and physiological responses to hypoglycemia.

During hypoglycemia, cerebral blood flow (CBF) does not increase significantly until peripheral glucose levels are very low (2.0 mmol/l), that is, well below the blood glucose threshold for impairment of cognitive function (3.0 mmol/l). Because increased rates of cerebral blood flow will increase glucose transport, a failure of flow to rise earlier, before brain function is threatened, might be considered maladaptive. To examine the influence of inducing an earlier rise in CBF during hypoglycemia, eight healthy volunteers participated in three studies using a randomized, placebo-controlled design. In all three studies, a hyperinsulinemic (60 mU x m2 x min(-1)) clamp was used to maintain blood glucose levels at 4.5 mmol/l for 60 min. Thereafter, for EUG-ACZ, blood glucose was maintained at 4.5 mmol/l from 60 to 170 min and at 90 min from the start of this study, and 1-g acetazolamide i.v. was given to induce an early rise in CBF; for HYPO-ACZ, glucose was lowered over 20 min to 2.8 mmol/l and kept at that level for 90 min, and acetazolamide was given 90 min from the start of this study; and for HYPO-CON, glucose was treated as in HYPO-ACZ, and matching placebo was given in place of acetazolamide. Injection of acetazolamide was associated with a 30% rise in right (95% CI 24-34%) and left (20-32%) middle cerebral artery velocity (an index of CBF) during euglycemia without any change in hypoglycemia awareness or counterregulatory hormone levels. When glucose was lowered to 2.8 mmol/l, acetazolamide caused a similar rise in middle cerebral artery velocity in the HYPO-ACZ study. However, all subjects were less "aware" of hypoglycemia, had fewer adrenergic symptoms (sweating, palpitations, tremors; all P < 0.05), and had lower plasma epinephrine levels (1,026 vs. 1,790 pmol/l; -764 [437 to 1,097] pmol/l, point estimate of difference [95% CI]; P < 0.001), compared with the HYPO-CON study, whereas levels of other counter-regulatory hormones and norepinephrine were similar. Cognitive function (latency of the P300 evoked response) was unaffected by increasing CBF. In conclusion, enhanced rates of cerebral blood flow at the onset of systemic hypoglycemia are associated with diminished perception of low blood glucose levels and attenuation of the epinephrine counterregulatory response. These findings suggest that augmenting cerebral blood flow leads to an enhanced rate of substrate delivery to the central nervous system.

Acetazolamide↗
PubMed1999

Luminal acid in water-immersion stress and the antiulcer effect of axetazolamide in the rat gastric mucosa.

The influence of water-immersion stress on gastric acid secretion, and the effect of acetazolamide (a potent carbonic anhydrase inhibitor) on acid secretion, and gastric mucosal lesion formation in rats under water-immersion stress were studied. Acid secretion in pylorus-ligated rats decreased under a 10_h stress period as compared with that of rats under normal conditions. Intraperitoneal administration of acetazolamide (100, 50, 25 mg/kg every 5 h for a total of two times) which significantly inhibited acid secretion in a dose-dependent fashion of stressed rats, prevented the development of gastric mucosal lesions produced by stress. Non antisecretory dose of acetazolamide (5 mg/kg, intraperitoneal administration every 5 h for a total of two times) did not prevent the formation of gastric mucosal lesions. Stress ulcer aggravation by acid administration (150 mM HCl, 0.5 ml/h) into the stomach during the stress was not prevented by treatment with antisecretory acetazolamide dose. We conclude that: (1) the exposure of rats to water-immersion stress for 10 h decreases gastric acid secretion, and (2) acetazolamide suppresses water-immersion stress-induced gastric lesions by inhibiting acid secretion.

Acetazolamide↗
PubMed1983

Contribution of matrix carbonic anhydrase to citrulline synthesis in isolated guinea pig liver mitochondria.

Synthesis of citrulline from ornithine, NH4+, and HCO3- by isolated pig liver mitochondria is inhibited by acetazolamide, a specific inhibitor of carbonic anhydrase, at the same concentrations which inhibit the mitochondrial matrix carbonic anhydrase. At an acetazolamide concentration sufficient to give complete inhibition of matrix carbonic anhydrase, the rate of citrulline synthesis is reduced by 71%, but no further decrease in citrulline is observed at higher concentrations of acetazolamide. Stimulation of O2 uptake by ornithine under conditions of maximal citrulline synthesis is also inhibited by acetazolamide. At pH 6.7, the ratio of citrulline synthesis is depressed relative to the rates observed over the range 7.2-7.7, and acetazolamide inhibits this rate by only 20%. These results support the hypothesis that the physiological role of carbonic anhydrase in liver mitochondria is to supply HCO3- as the substrate for the enzyme carbamoyl phosphate synthetase I, which provides the intermediate carbamoylphosphate in the rate-limiting step of citrulline synthesis. Since the uncatalyzed rate of CO2 hydration is rapid enough that it should not be rate-limiting for the carbamoylphosphate synthetase reaction, carbonic anhydrase appears to regulate access of HCO3- in the synthetase and so should be considered as one of the enzymes participating in the biosynthetic pathway leading to urea formation in the hepatocyte.

Acetazolamide↗
PubMed1984

Carbonic anhydrase independent bicarbonate reabsorption in rats with chronic papillary necrosis.

The present study was designed to indirectly localize the tubular sites of carbonic anhydrase independent bicarbonate reabsorption in the rat. Papillary necrosis was induced in rats by intravenous administration of bromoethyleneamine hydrobromide (BEA) 6 weeks prior to the study, in order to assess the role of deep nephrons in this process. Acetazolamide alone, acetazolamide plus amiloride, and acetazolamide, amiloride plus furosemide were infused into rats with intact papillae (groups I, III, V) and rats with BEA-induced papillary necrosis (groups II, IV, VI). Our results show that chronic papillary necrosis does not alter carbonic anhydrase independent bicarbonate reabsorption, since the fractional excretion of bicarbonate (FEHCO3) was not significantly higher when acetazolamide was infused into animals with BEA-induced papillary necrosis as compared to those rats with intact papillae (FEHCO3 group I vs. group II: NS). The addition of amiloride hydrochloride, a blocker of distal acidification at the administered doses, increased FEHCO3 significantly in both, animals with intact papillae and those with papillary necrosis, to a similar degree. The addition of furosemide to acetazolamide and amiloride further induced a significant increase in FEHCO3 only in the group of animals with papillary necrosis (FEHCO3 group V 43.0 +/- 2.9% vs. group VI 52.1 +/- 0.9%; p less than 0.05). It appears from our study that deeper nephrons and papillary structures are not indispensable for carbonic anhydrase independent bicarbonate reabsorption in the rat on a chronic basis. The cortical collecting duct appears to have a significant capacity to reabsorb bicarbonate independent of carbonic anhydrase which can be blocked by amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1994

Effect of MK-507 on aqueous humor dynamics in normal human eyes.

The effects of the topical carbonic anhydrase inhibitor, MK-507, on aqueous humor dynamics were studied in 6 normal volunteers. As a baseline study, intraocular pressure (IOP) was determined and aqueous protein concentration was checked hourly by laser flare-cell photometry from 0900 to 1800 hours. One week later, IOP and aqueous protein concentration were determined in the same subjects on the same time schedule with instillation of 1% MK-507 at 1100 hours. After one more week, the same experiment was carried out with oral administration of acetazolamide at a dose of 250 mg at 1100 hours. Topical MK-507 showed the maximum IOP reduction at 3 hours and increased aqueous protein concentration reaching its maximum at 4 hours. Oral acetazolamide showed the maximum IOP reduction at 2 hours and the maximum increase in aqueous protein concentration was at 3 hours. Although the peak effect on IOP or aqueous protein concentration did not significantly differ between topical MK-507 and oral acetazolamide, only oral acetazolamide showed a significant effect at 1 hour. These results suggested that topical MK-507 reduced the aqueous humor production, but it took more time for the ocular effect to become manifest than after administration of oral acetazolamide.

Acetazolamide↗
PubMed1994

Cerebral blood flow study in patients with moyamoya disease evaluated by IMP SPECT.

UNLABELLED: We studied the usefulness of IMP SPECT with acetazolamide in 16 patients with moyamoya disease. Cerebral angiography was performed for all patients who were classified in three grades according to their angiographic stages. METHODS: Techniques used included ring-type emission computed tomography with a minicomputer system. Patients received 111 MBq of 123I-IMP and SPECT images were obtained 20 min postinjection. Nine patients were studied using iodoamphetamine (IMP) SPECT with and without acetazolamide. IMP SPECT with acetazolamide was performed 20 min after each injection of 1 g of acetazolamide. RESULTS: Low perfusion areas in the upper and lower frontal, parietal and temporal regions in grades 2 and 3 using IMP SPECT were observed. The mean cerebral-to-cerebellar activity ratios (C/C ratio) of six regions (upper and lower frontal, temporal, parietal occipital and basal ganglia) in grades 1, 2 and 3 were 0.96 to 1.06, 0.91 to 0.96 and 0.76 to 0.88, respectively. CONCLUSION: Our results indicate that measurement of regional cerebral blood flow (rCBF) elucidates cerebral hemodynamic factors, including the reactivity of cerebral vessels which cannot be detected angiographically in patients with moyamoya disease, and that the acetazolamide test is useful for detecting cerebral blood flow reserve. The test can be used to detect disease progress prospectively.

Acetazolamide↗
PubMed1996

Membrane-bound carbonic anhydrase activity in the rat corneal endothelium and retina.

Localization of carbonic anhydrase (CA) was investigated in the rat eye by light and electron microscopy, and the inhibitory effects on CA distribution in the rat eye were compared between dorzolamide and acetazolamide. The cobalt sulfide histochemical method was used to study the CA localization. Acidic osmification was carried out for postfixation of the electron microscopic observations. The inhibition of CA activity was examined with different concentrations of acetazolamide and dorzolamide. The cytoplasm, lateral cell membranes and karyoplasm of the corneal endothelium showed CA activity. In the retina, the processes and cell bodies of Müller cells, the tips of the outer segments of the rods, and apical villi and basolateral membranes of the pigment epithelium indicated CA activity. CA activity was inhibited by dorzolamide at lower concentrations than needed for acetazolamide and only the CA activity of the nerve fiber layer remained at 10(-6) M of acetazolamide and 5 x 10(-7) M of dorzolamide. The presence of membrane-bound CA activity was confirmed in the corneal endothelium and Müller cells. CA activity was also demonstrated in the apices of rod outer segments and scleral fibroblasts. The CA inhibition test revealed that dorzolamide was a stronger CA inhibitor than acetazolamide and that the CA activity of the nerve fiber layer was strongest in the rat eye.

Acetazolamide↗