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At least 1,207 records · Page 67Linked to original sources
PubMed1996

[A comparative study of intravenous opioid analgesia. Sufentanil and alfentanil for extracorporeal shock-wave lithotripsy in urologic patients].

UNLABELLED: Extracorporeal shock-wave lithotripsy (ESWL) is the method of choice for the treatment of solitary stones in the kidney or ureter. Early lithotripters required prolonged immobility of the patient and caused considerable pain, necessitating general or epidural anaesthesia during the procedure. Modern lithotripters are quicker, but still require analgesia. Intravenous opioids are currently the drugs in favour. The opioids most commonly used are fentanyl and its shorter-acting analogue, alfentanil. The latter has a more rapid onset and, because of its reduced lipid solubility, is less cumulative. Sufentanil is a new opioid that is also of the phenylpiperidone group and has been recently licensed and introduced in Germany. Its pharmacokinetic and pharmacodynamic properties suggest an intermediate duration of action, high analgesic potency, and cardiovascular stability with diminished respiratory depression. In this prospective double-blind study, the effects of alfentanil and sufentanil on cardiovascular and respiratory parameters, the quality of analgesia, degree of sedation and the number and type of side-effects were compared. PATIENTS AND METHODS: After giving informed consent and with the approval of the hospital ethics committee, 62 patients (ASA I or II) were investigated. They were randomly allocated to two groups, either receiving sufentanil (n = 32) or alfentanil (n = 30) during ESWL. No premedication was given. Excluded were patients with pain prior to treatment, patients treated with a spasmolytic or analgesic drug and those who had undergone ESWL within the last 6 months. The loading dose was given as a 5-min infusion to each group. The heart rate, systolic and diastolic blood pressure, percutaneous oxygen saturation (SpO2), and the transcutaneous capillary carbon dioxide tension (PicCO2) were recorded prior to the procedure (i.e. before administration of opioid), after 1000 and after 2000 shock waves and then 1 and 2 h after the end of lithotripsy. After 1000 and 2000 shock waves, and 1 an 2 h after the treatment, the patients were asked to express their degree of tiredness and pain on a visual analogue scale (VAS). The occurrence of side-effects such as nausea, vomiting, pruritus or other unpleasant sensations were noted by an anaesthesia nurse. Simultaneously, the anaesthetist recorded his/her impression of the patient's tiredness and degree of pain, both by using the VAS. He was not allowed to question the patient, nor was he aware of the patient's own scores. At the end of the observation period both the patient and the anaesthetist related their overall satisfaction with the anaesthetic procedure, again by using the VAS. Data were analysed with the Mann-Whitney-U for comparisons between groups and with the Wilcoxon test within each group. The side-effects were analysed with the Chi-square test. RESULTS: The systolic and diastolic blood pressure remained stable in both groups during and after treatment. The mean heart rate was different between the two groups at the beginning, and after the end of the treatment it dropped in both groups, but no significant difference was seen between groups. The PicCO2 rose from an initial mean of 36.8 mm Hg to a maximum of 44.6 mm Hg after 1000 shock waves in the sufentanil group, and from 37.8 mm Hg to 46.0 mm Hg after 2000 shock waves in the alfentanil group. The differences were significant within groups until 1 h after the end of the treatment, but there was no significant difference between groups. The oxygen saturation SpO2 dropped slightly in both groups. The differences were not significant between groups. In the alfentanil group, one patient had a maximum carbon dioxide tension of 83 mm Hg after 2000 shock waves, whereas in the sufentanil treated group the oxygen saturation fell to 72% in one case. (ABSTRACT TRUNCATED)

Alfentanil↗
PubMed2001

[Postoperative pain therapy in pediatrics. Results of a representative survey in Germany].

The last survey addressing postoperative pain management in Germany was published in 1987, special data concerning postoperative pain management in pediatric patients had not been presented previously. The goal of this survey is to present the standard of postoperative pain management in pediatric patients in Germany. A detailed questionnaire was mailed to all German anaesthesia departments and interdisciplinary intensive care units (n = 1,500) to determine the current management of postoperative pain management in pediatric patients. After eight weeks, 42.6% of the survey had been returned. Rectally administered acetaminophen is the standard drug regimen for postoperative analgesia in children. Compared to previous surveys, the use of opioids has increased in popularity. The routine use of non-steroid antiinflammatory drugs (NSAIDs) and spasmolytics as well as the application of regional anaesthesia techniques is uncommon in pediatric postoperative pain management. Compared to other European countries, patient- or parent-controlled analgesia is more popular in Germany. Despite modern concepts of organization and a great variety of drugs available today, 71.1% of the responding anesthesiologists in this survey still believe that pediatric postoperative pain management needs to be improved.

Analgesics↗
PubMed2006

[Drug therapy for irritable bowel syndrome. What works, what doesn't work and for whom?].

The therapy of patients with irritable bowel syndrome (IBS) is often challenging, especially if a broad spectrum of symptoms is present and trigger factors, such as the influence of diet or stress, are lacking. Current pathogenetic concepts propose central or peripheral alterations that cause disturbed gastrointestinal function (motility, visceral sensitivity) and subsequent symptoms. These alterations are possibly related to psychological (stress, depression, anxiety) and biological (post-infectious residuals, micro-inflammation) influences. Since no universally effective medical treatment is available to treat the causes of the disease, standard medical therapy is symptom directed (especially for pain, constipation and diarrhoea). In addition to well established drugs (like spasmolytics, opioids and laxatives), newly developed compounds including those with other primarily indications (e.g. antidepressants) are available for highly differentiated individualized therapies. New medical approaches which are currently undergoing evaluation, promise further progress in the treatment of IBS.

Antidepressive Agents, Tricyclic↗
PubMed2005

[CT of acute left-sided colonic diverticulitis and its differential diagnoses].

PURPOSE: This review shows the diagnostic potential of computed tomography (CT) in the diagnosis and differential diagnosis of acute left-sided colonic diverticulitis. METHODS: Using a single detector spiral CT, standard examination of the entire abdomen is performed after oral and rectal administration of diluted iodinated contrast medium with collimation of 8 mm, pitch of 1.5, and reconstruction increment of 8 mm before and after intravenous contrast injection. Intravenous administration of spasmolytic agents, various patient positions, and the thin-section technique with 3-5 mm slices are beneficial in difficult cases. RESULTS: The differential diagnosis of acute left-sided colonic diverticulitis includes tumorous, inflammatory, and ischemic diseases of the colon as well as infarctions of epiploic appendages and the omentum majus. The knowledge of the various CT criteria of acute colonic diverticulitis and their differential diagnoses helps to establish a correct diagnosis in a wide majority of cases. CONCLUSION: At present, CT is the diagnostic procedure of choice for assessing acute diverticulitis. Distinct knowledge of the CT features helps to differentiate the various entities accurately.

Acute Disease↗
PubMed1997

[Injection treatment of non-radicular lumbalgia].

Low back pain is the most expensive condition in industrialized countries. Approximately 65-80% of the population will be afflicted with low back pain at some point during their life. Low back pain has many causes and can originate from any of several pain-sensitive foci, among which are facet joints, sacroiliac joint, muscle and ligaments. Primary care in the acute phase consists of nonsteroidal anti-inflammatory drugs to address the biochemical and inflammatory mediators of pain or skeletal muscle spasmolytics to reduce low back pain symptoms. Injection procedures should be reserved for the patients with low back pain who fail to respond to a directed, conservative treatment trial and have had pain for at least 2 weeks duration. Eliminating sensation from a certain pain source has been proposed as a way to allow an examiner to determine if that joint is responsible for the patient's pain. Injections of local anesthetic into the facet joint or around its nerve supply are clinical methods of eliminating pain from focal areas such as facet joints or myofascial trigger points. When a particular joint is determined to be the source of pain, long-term relief can be sought by directing therapeutic interventions at that joint. The anatomic accessibility of the most common pain sources of low back pain make diagnostic blocks and therapeutic instillation of corticosteroids particularly appealing. If used, their potential benefit for the individual case needs to be carefully weighed. They should be used to facilitate more aggressive conservative care and not as an isolated treatment. Certainly, if response to corticosteroids does not occur after the first injection, no further administration of corticosteroids is indicated.

Adrenal Cortex Hormones↗
PubMed2006

Propiverine and metabolites: differences in binding to muscarinic receptors and in functional models of detrusor contraction.

Propiverine is a commonly used antimuscarinic drug used as therapy for symptoms of an overactive bladder. Propiverine is extensively biotransformed into several metabolites that could contribute to its spasmolytic action. In fact, three propiverine metabolites (M-5, M-6 and M-14) have been shown to affect various detrusor functions, including contractile responses and L-type calcium-currents, in humans, pigs and mice, albeit with different potency. The aim of our study was to provide experimental evidence for the relationship between the binding of propiverine and its metabolites to human muscarinic receptor subtypes (hM(1)-hM(5)) expressed in chinese hamster ovary cells, and to examine the effects of these compounds on muscarinic receptor-mediated detrusor function. Propiverine, M-5, M-6 and M-14 bound to hM(1)-hM(5) receptors with the same order of affinity for all five subtypes: M-6 > propiverine > M-14 > M-5. In HEK-293 cells expressing hM(3), carbachol-induced release of intracellular Ca(2+) ([Ca(2+)](i)) was suppressed by propiverine and its metabolites; the respective concentration-response curves for carbachol-induced Ca(2+)-responses were shifted to the right. At higher concentrations, propiverine and M-14, but not M-5 and M-6, directly elevated [Ca(2+)](i). These results were confirmed for propiverine in human detrusor smooth muscle cells (hDSMC). Propiverine and the three metabolites decreased detrusor contractions evoked by electric field stimulation in a concentration-dependent manner, the order of potency being the same as the order of binding affinity. We conclude that, in comparison with the parent compound, loss of the aliphatic side chain in propiverine metabolites is associated with higher binding affinity to hM(1)-hM(5) receptors and higher functional potency. Change from a tertiary to a secondary amine (M-14) results in lower binding affinity and reduced potency. Oxidation of the nitrogen (M-5) further lowers binding affinity as well as functional potency.

Animals↗
PubMed1997

The clinical pharmacology of single doses of otilonium bromide in healthy volunteers.

OBJECTIVE: Otilonium is a smooth muscle spasmolytic with greater affinity for receptors in the smooth muscle of distal than proximal gut in rats. This study was the first to compare distal and proximal GI transit effects in human subjects. METHODS: Using an increasing dose design for the safe exploration of clinical and supraclinical single dose levels, two groups of eight volunteers received either 40, 120 and 200 mg or 80, 160 and 240 mg otilonium. Gastric emptying of 400 ml 10% glucose solution was assessed by epigastric impedance (EI), orocaecal transit time (OCTT) by the lactulose breath-hydrogen method and whole gut transit time (WGTT) by the method of Hinton et al. [1]. Potential anticholinergic effects were assessed via visual accommodation using the RAF rule and saliva flow in response to sucking a sweet. RESULTS: Median WGTT after 120 mg significantly increased by 4.1 h relative to placebo, but at higher doses median changes relative to placebo were not significant due to wide increases in group variance. The EI t50% was delayed by 1.4 min when results from the two highest doses were combined and compared with placebo; this small difference was statistically significant but seems unlikely to achieve physiological or clinical significance. OCTT, visual accommodation and saliva flow were unaltered. Otilonium bromide was well tolerated at all doses, due mainly to low systemic absorption.

Accommodation, Ocular↗
PubMed1996

Cloning of contiguous genomic fragments from human chromosome 21 harbouring three trefoil peptide genes.

A group of small peptides with a typical cysteine-rich domain (termed trefoil motif or P-domain) is abundantly expressed at mucosal surfaces of specific normal and neoplastic tissues. Their association with the maintenance of surface integrity was suggested. The first known human trefoil peptide (pS2) was isolated from breast cancer cells (MCF7). Its oestrogen-inducible gene, and the human homologue to the porcine spasmolytic peptide gene (hSP/SML1) appear synchronously expressed in healthy stomach mucosa and several carcinomas of the gastrointestinal tract. Both genes were shown to be localised at 21q22.3. A new trefoil peptide from human intestinal mucosa (hITF/hP1.B) and its gene were described recently. By using suitable oligonucleotide primers and PCR and isolating large (110-250 kb) genomic recombinants cloned in the bacterial artificial chromosome (BAC) system, we present a genomic region from chromosome band 21q22.3 cloned in contiguous sequences and encoding all three members of human P-domain/trefoil peptides proving a physical linkage of all three trefoil peptide genes. Such genomic sequences will provide useful experimental material for analysis of gene regulation, for gene modification experiments and for establishing transgenic cells or animals.

Base Sequence↗
PubMed1998

[Ketorolac and butylscopolamine in combination with alfentanil for renal lithotripsy].

BACKGROUND: Patient-controlled analgesia (PCA) using intravenous alfentanil provides adequate pain relief during extracorporal shock wave lithotripsy (ESWL) of renal stones. Occasional disadvantages of opioid analgesia include nausea, sedation and respiratory depression. This double-blind, placebo-controlled study examined whether the alfentanil requirements and thereby the frequency of side effects could be reduced by preemptive analgesia with the non-opioid analgesic ketorolac or the spasmolytic butylscopolamine. METHODS: 90 patients scheduled for ESWL of renal stones received 1 hour prior to ESWL ketorolac 30 mg, butylscopolamine 20 mg or placebo intramusculary. 10 mg of metoclopramide and 6.6 microg/kg of alfentanil were given intravenously at the beginning of ESWL (Philips/Dornier MFL 5000). Intravenous PCA was started (demand dose: 0.25 mg of alfentanil, lockout time: 1 minute). Pain intensity (NRS 0-100), sedation score (VRS 0-4), respiratory rate (min(-1)) and partial oxygen saturation (SO(2)) were measured every 5 minutes. Statistical analysis included ANOVA and Chi-square-test (p<0,05). RESULTS: Demographic and ESWL data were comparable between the study groups. However, patients of the ketorolac group were statistically significantly younger than those in the other groups. Alfentanil doses, pain scores and frequency of respiratory depression, sedation and nausea were lower subsequent to ketorolac than subsequent to butylscopolamine or placebo (not statistically significant). Signs of respiratory depression were only seen during ESWL. CONCLUSIONS: The present study confirms that PCA using alfentanil is effective during ESWL of renal stones. However, because of the possibility of respiratory depression, adequate monitoring is mandatory. Preemptive analgesia with 30 mg of ketorolac or 20 mg of butylscopolamine cannot reduce alfentanil requirements or improve efficacy and safety.

Clinical Trial↗
PubMed2005

Ischemic colitis following colonoscopy in a systemic lupus erythematosus patient: report of a case.

BACKGROUND: Ischemic colitis is an uncommon complication in patients with systemic lupus erythematosus but may be precipitated by colonoscopy. CASE REPORT: A 43-year-old female with systemic lupus erythematosus under treatment with immunosuppressive drugs and prednisone was submitted to colonoscopy because of a change in bowel habit. Apart from the presence of a small metaplastic polyp, colonoscopy showed only a few erythematosus areas in the sigma and left colon. Four hours after colonoscopy, the patient developed lower colic abdominal pain and mucous diarrhea followed by rectal bleeding from ischemic colitis. The patient was successfully treated with fluids, spasmolytic drugs, sodic heparin, antibiotics and enteral feeding. CONCLUSIONS: Awareness of the risk of this potential complication, secondary to colonoscopy, in patients with connective tissue disorders may lead to a prompt diagnosis and effective treatment, with a successful outcome.

Adult↗
PubMed2005

Virtual colonoscopy: clinical application.

Virtual colonoscopy (VC), also known as computed tomography Colonography (CTC), is a non-invasive test for the examination of the colon based on volumetric, thin-collimation CT acquisition of a cleansed and air-distended colon. The technique is easy, less labour-intensive than barium enema and conventional colonoscopy, and is inherently safer. Several studies demonstrate the ability of VC in the detection of colonic neoplastic lesions, not only large carcinomas, but also polyps. Currently, the most widely accepted clinical indication is incomplete or unsuccessful colonoscopy, which may be the result of redundant colon, patient intolerance to the procedure, spasm not resolving even with the use of spasmolytics, obstructing colo-rectal cancer. VC is also used to detect cancer in frail and immobile patients to avoid sedation during colonoscopy or the turning required during barium enema. The use of VC in patients under surveillance following colo-rectal cancer surgery is under investigation. Further studies are necessary in order to assess the cost-effectiveness of this approach. For colo-rectal cancer screening, a practical approach is to consider VC as a currently credible alternative screening method and as a reasonable alternative to the other colo-rectal cancer screening tests when a patient is unable or unwilling to undergo conventional colonoscopy.

Clinical Trials as Topic↗
PubMed2006

Omeprazole treatment ameliorates oxyntic atrophy induced by DMP-777.

Atrophic gastritis, characterized as parietal cell loss or oxyntic atrophy, is the primary event in the evolution of the spectrum of metaplastic and hyperplastic lineage changes thought to predispose to gastric neoplasia. A number of animal models have provided insights into the lineage changes induced by oxyntic atrophy. Recently, we have reported a model for pharmacological induction of oxyntic atrophy with DMP-777. DMP-777 ablates parietal cells selectively and leads to the gastric cell lineage changes including foveolar hyperplasia and spasmolytic polypeptide expressing metaplasia (SPEM). Previous investigations showed that DMP-777 dissipated a gastric tubulovesicle proton gradient without impairing the H/K-ATPase activity, consistent with its pharmacological action as a parietal cell-specific protonophore which could induce parietal cell necrosis through backwash of luminal acid into actively secreting cells. We hypothesized that, if DMP-777 was acting as a parietal cell protonophore, then suppression of acid secretion should protect parietal cells from the toxic effects of the drug. In this study, we pretreated and coadministered the proton pump inhibitor omeprazole with DMP-777 to determine the effect of active acid secretion inhibition on the DMP-777-induced histologic changes in the stomachs of male rats. Omeprazole pretreatment ameliorated DMP-777-induced parietal cell loss as well as foveolar hyperplasia. These results indicate that active acid secretion is required for DMP-777 cytotoxicity, consistent with its suggested behavior as a parietal cell-specific protonophore.

Analysis of Variance↗
PubMed2004

Treatment of Excessive Intestinal Gas.

Symptoms of excessive intestinal gas may be related to eructation, excessive or odoriferous gas evacuation, and/or abdominal symptom attributed to gas retention. Patients with aerophagia and excessive eructation can be usually retrained to control air swallowing, but if present, basal dyspeptic symptoms may remain. Patients with excessive or odoriferous gas evacuation may benefit from a low-flatulogenic diet. In patients with gas retention due to impaired anal evacuation, anal incoordination can be resolved by biofeedback treatment, which also improves fecal retention, and thereby reduces the time for fermentation. Other patients complaining of abdominal symptoms that they attribute to intestinal gas, probably have irritable bowel syndrome or functional bloating, and their treatment options specifically targeting gas-related symptoms basically include prokinetics and spasmolytics. There is no consistent evidence to support the use of gas-reducing substances, such as charcoal or simethicone.

Journal Article↗
PubMed1982

Efficacy of chronic amiodarone therapy in patients with variant angina pectoris and inhibition of ergonovine coronary constriction.

In three patients with vasospastic angina pectoris, chronic amiodarone administered orally at doses of 800 and 1,000 mg/day totally suppressed spontaneous episodes of ischemic chest pain for 8 to 14 months. Before treatment, ergonovine maleate 0.2 to 0.4 mg intravenously provoked chest pain and similar ischemic ECG changes as those occurring spontaneously. During amiodarone treatment ergonovine vasoconstriction was totally or partially inhibited. In addition to calcium-blocking agents, amiodarone is another spasmolytic drug which effects smooth muscle relaxation by different mechanisms and appears to be useful for the chronic treatment and prevention of variant angina. The vasodilator property of amiodarone is achieved by both direct action and noncompetitive alpha receptor antagonism of coronary vasculature.

Administration, Oral↗
PubMed1985

Experimental basis of the long-term therapy of arterial hypertension with calcium antagonists.

In vascular smooth muscle (as in myocardial fibers) a transmembrane supply of Ca++ ions is required for active tension development. In consequence, Ca++ antagonists, which restrict transmembrane Ca++ delivery, possess a wide scope of action against practically all types of vasoconstrictor or spastic reactions on coronary, pulmonary, cerebral, renal or mesenteric arteries. Another important target of Ca++ antagonists is the resistance vessels of systemic circulation in both animals and humans. Thus, Ca++ antagonists are successfully used for the treatment of acute hypertensive crises as well as for long-term antihypertensive therapy. Spontaneously hypertensive rats (SHRs) also respond to suitable Ca++ antagonists with a dramatic fall in blood pressure. The acute spasmolytic effects of Ca++ antagonists can be directly visualized by ophthalmoscopic examination of the arterioles in the ocular fundus. In untreated SHRs these arterioles are always heavily constricted, and aneurysm-like luminal protuberances develop. In contrast, after 1 adequate Ca++ antagonist dose, blood pressure instantaneously falls to its normal level while the retinal arterioles dilate. A further important effect of Ca++ antagonists that we have demonstrated in experiments on SHRs is the prevention of progressive arterial Ca++ overload, which otherwise produces severe calcinotic or arteriosclerotic damage of the arterial walls. However, with the help of Ca++ antagonists, arterial integrity can be totally preserved. Interestingly, this anticalcinotic arterial protection by Ca++ antagonists may also manifest itself independent of any blood pressure change. This is true of arterial calcinosis in normotensive rats because of advanced age, alloxan diabetes or intoxication with overdoses of vitamin D3, dihydrotachysterol or nicotine.

Animals↗
PubMed1989

Effect of nicorandil on coronary spasm.

In patients in whom dynamic coronary obstruction plays a predominant role in the pathogenesis of angina pectoris, dilatation of large coronary arteries and relief of coronary spasm account for the main mechanism of action of antianginal drugs. In this study, the acute vasodilating effects of nicorandil, a newly developed antianginal drug, were assessed in 10 patients who had spontaneous and ergonovine-evoked coronary spasms. The prompt, complete relief of both spontaneous and evoked coronary spasms was obtained in all of 10 patients with nicorandil. The coronary spasmolytic effect of nicorandil in the present series is thus considered to be beneficial to the treatment of coronary spasm.

Adult↗
PubMed1996

Use of verapamil and nitroglycerin solution in preparation of radial artery for coronary grafting.

BACKGROUND: The radial artery (RA) has been used as an alternative arterial graft for coronary artery bypass grafting. This artery has been reported to be spastic; therefore, use of spasmolytic drugs (vasodilators) during the preparation of the RA is recommended. The combination of calcium antagonists and nitroglycerin (verapamil plus nitroglycerin, VG solution) has been suggested to be effective in other bypass grafts. This study was designed to investigate (1) the effect of the VG solution during preparation of the RA for coronary artery bypass grafting and (2) whether the effect would last for a prolonged period after topical use. METHODS: Ring segments of the RA taken from coronary artery bypass grafting patients were studied in organ chambers at a physiologic pressure. The relaxation effect of VG (30 mumol/L verapamil and 30 mumol/L nitroglycerin, n = 5) or papaverine (30 mumol/L, n = 5) was recorded in K+ (25 mmol/L potassium chloride)-precontracted RA segments. Other segments taken from the RA were treated (n = 5) or not treated (n = 20, as the control) with the VG solution for 45 minutes before used for coronary artery bypass grafting. Both the VG-treated and nontreated segments were immersed in oxygenated Krebs solution and stored in a refrigerator at 4 degrees C for 24 hours. The contraction force to 100 mmol/L K+ was compared between the two groups. RESULTS: The VG solution induced more rapid relaxation than papaverine (p < 0.05 from the first to the ninth minute). After 10 minutes, both solutions induced full relaxation. The contraction to K+ (100 mmol/L) in rings treated with VG solution for 45 minutes during operation was almost abolished 24 hours later (0.86 +/- 0.1 g). In contrast, the control segments (n = 20) taken from nontreated RA contracted with K+ to high force (5.0 +/- 0.6 g; p < 0.001). CONCLUSIONS: The present study suggests that the combination of verapamil and nitroglycerin may provide a rapid onset, a complete relaxation, and a long-lasting vasorelaxant effect when used to prepare the RA for grafting. This study adds a new method to prevent RA spasm during coronary artery bypass grafting.

Coronary Artery Bypass↗
PubMed1983

Tissue and substrate specificity of inhibition by alkoxy-aryl-lactams of platelet and arterial smooth muscle cyclic nucleotide phosphodiesterases relationship to pharmacological activity.

Alkoxy-aryl-lactams (cilostamide, AAL 05, ZK 62 711, Ro 20-1724) inhibit differently cAMP or cGMP phosphodiesterases from blood platelets or vascular smooth muscle. Cilostamide (IC50 0.23 microM) and AAL 05 (IC50 0.15 microM) are 100 times more potent towards platelet cAMP phosphodiesterase whereas ZK 62 711 (IC50 2 microM) and Ro 20-1724 (IC50 33 microM) inhibit more selectively the enzyme from aorta. The substrate specificity of the inhibitors is different in the two tissues: ZK 62 711 and cilostamide are respectively 345 and 290 times more potent as inhibitor of cAMP than cGMP phosphodiesterase from vascular smooth muscle (ZK 62 711) or platelets (cilostamide). M + B 22,948 selectively inhibits cGMP phosphodiesterase with an IC50 of 9 or 24 microM on platelet or aorta enzyme, respectively. In general, the potencies of spasmolytic and platelet inhibitor effects vary from one drug to the other with the potency of inhibition of phosphodiesterase from the corresponding tissue. These data suggest that phosphodiesterases from platelets are different from those of arterial smooth muscle.

3',5'-Cyclic-AMP Phosphodiesterases↗