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PubMed2004

Pediatric sleep pharmacology: you want to give my kid sleeping pills?

There is a need for greater information about the pharmacologic management of sleep disorders in children. Pharmacologic guidelines must be developed specifically for sleep disorders in children. Ideally, these guidelines should be approved by the Food and Drug Administration for a specific sleep disorder or for the pediatric age range. This approval prevents physicians from being forced to prescribe medications as an "off label" indication. Development of easy-to-swallow, chewable, or liquid forms of these medications would be well received by parents everywhere. When these are not available, instructions for compounding these medications into a suspension by pharmacists are needed. Integration of behavioral and pharmacologic treatments may yield better patient outcomes. This approach requires pediatricians to have a comprehensive understanding of clinical sleep disorders in children. Training programs should play the lead role in enhancing pediatricians' knowledge of the pharmacologic treatment of sleep disorders in children.

Benzodiazepines↗
PubMed1991

Pharmacologic challenges for establishing interspecies extrapolation models in neurotoxicology.

Pharmacologic challenges and dose/response studies are discussed as tools for aiding in the extrapolation of nonhuman animal models to human neurotoxicology. Specific experiments conducted using humans, baboons, rhesus monkeys, and dogs are cited as examples of the use of pharmacologic methods for neurotoxicology applications. Respiratory sinus arrhythmias are quantified following atropine sulfate administration and the resulting vagolytic blockade is used as a pharmacologic challenge technique. Dose/response studies in humans and rhesus monkeys are cited as an example for interspecies comparisons using ED50 calculations for a 30% decrease in the respiratory sinus arrhythmias following atropine. Pharmacologic challenges with drugs of relevant mechanisms of action are useful for demonstrating relative physiologic responses for interspecies extrapolations.

Animals↗
PubMed2000

Adventures in the pharmacological analysis of P2 receptors.

The pharmacological classification of P2 receptors owes its origin to the pioneering efforts of Geoff Burnstock and those who followed him, research that was conducted primarily in physiological experimental systems. Over recent years, the techniques of molecular biology have been increasingly applied in the study of P2 receptors while, at the same time, advances in their pharmacological analysis have been limited by a lack of potent and selective agonist or antagonist ligands. This has resulted in a classification scheme which is largely structural in nature, with relatively little contribution from pharmacology. Our endeavours in this area have been directed towards the discovery of ligands with which the pharmacological analysis and definition of P2 receptors could be advanced, the ultimate goal being the design of therapeutic agents. This article will describe some of our experiences in this challenging but rewarding area.

Animals↗
PubMed1999

Pharmacological and biochemical interactions between opioids and cannabinoids.

Opioids and cannabinoids are among the most widely consumed drugs of abuse in humans. A number of studies have shown that both types of drugs share several pharmacological properties, including hypothermia, sedation, hypotension, inhibition of both intestinal motility and locomotor activity and, in particular, antinociception. Moreover, phenomena of cross-tolerance or mutual potentiation of some of these pharmacological effects have been reported. In recent years, these phenomena have supported the possible existence of functional links in the mechanisms of action of both types of drugs. The present review addresses the recent advances in the study of pharmacological interactions between opioids and cannabinoids, focusing on two aspects: antinociception and drug addiction. The potential biochemical mechanisms involved in these pharmacological interactions are also discussed together with possible therapeutic implications of opioid-cannabinoid interactions.

Cannabinoids↗
PubMed2002

Pharmacological characterization of vanilloid receptor located in the brain.

Specific [3H]resiniferatoxin (RTX) binding detects the vanilloid receptor type I (VR1). In the present study we demonstrate specific, high-affinity, saturable [3H]RTX binding in various areas of monkey brain not known to be innervated by primary afferent neurons as well as in spinal cord and dorsal root ganglion neurons of the same origin. Detailed pharmacological characterization and comparison revealed no major difference in binding affinities between the peripheral and the central sites as measured by K(d)/K(i) values. In general, lower receptor density was measured in selected brain areas than in the periphery. Areas with higher receptor density were detected in the locus ceruleus, preoptic area, and medial basal hypothalamus of the brain. Both capsaicin and the competitive antagonist capsazepine inhibited the specific binding of [3H]RTX to membrane preparations of the dorsal horn of the spinal cord and dorsal root ganglia with K(i) values of 4.3+/-0.32 microM and 2.7+/-0.33 microM, respectively. Inhibition was observed in the central areas (hypothalamus) with K(i) values of 0.95+/-0.1 microM for capsaicin and 0.86+/-0.11 microM for capsazepine. Previous biological and pharmacological evidence suggested that vanilloid receptors were present in the brain. Our results demonstrate that the pharmacological properties of both the peripheral and central receptor sites display appropriate pharmacological similarity to represent the same receptor class. The modest differences in ligand affinities for the vanilloid receptor expressed in the brain nuclei and the dorsal root ganglion neurons may correspond to differences in sequence, modification or associated proteins.

Animals↗
PubMed2000

Update on pharmacologic therapy for chronic obstructive pulmonary disease.

As described throughout this article, significant improvements continue to occur in the pharmacologic management of COPD. These improvements range from improved medication targeting to better understanding of mechanisms of action, to better delivery of medications, to lower side effects. New areas of pharmacologic intervention, if not ready for use today, hold great promise for the not-too-distant future. In addition to the many agents described here, multiple mediator antagonists and anti-inflammatory agents are also under investigation for use in COPD. Interestingly, repair of alveolar tissue may be possible. Indeed, preliminary animal studies suggest that retinoic acid may be able to induce regeneration of lung alveoli. Overall, more effort is needed to broaden awareness and provide for the appropriate diagnosis of COPD, better explain pharmacologic therapies for COPD, simplify and disseminate guidelines, and highlight key differences between asthma and COPD, including their treatment strategies. As interest in COPD continues to grow, future updates on COPD management will continue to add new pharmacologic options for this devastating and preventable disease.

Adrenal Cortex Hormones↗
PubMed2003

Neuroprotective efficacy of pharmacological pretreatment and antidotal treatment in tabun-poisoned rats.

To study the influence of pharmacological pretreatment (PANPAL) and antidotal treatment (obidoxime plus atropine) on tabun-induced neurotoxicity, male albino rats were poisoned with a lethal dose of tabun (280 microg/kg i.m.; 100% of LD(50) value) and observed at 24 h and 7 days following tabun challenge. The neurotoxicity of tabun was evaluated using a functional observational battery (FOB) and an automatic measurement of motor activity. Pharmacological pretreatment as well as antidotal treatment were able to eliminate most of tabun-induced neurotoxic effects observed at 24 h following tabun poisoning. However, there was not significant difference between the efficacy of PANPAL and antidotal treatment to eliminate tabun-induced neurotoxicity in rats. The combination of PANPAL pretreatment and antidotal treatment seems to be slightly more effective in the elimination of tabun-induced neurotoxicity in rats at 24 h following tabun challenge in comparison with the administration of PANPAL pretreatment or antidotal treatment alone. At 7 days following tabun poisoning, very few neurotoxic signs in tabun-poisoned rats were observed regardless of administration of pharmacological pretreatment or antidotal treatment. Thus, our findings confirm that the combination of pharmacological pretreatment and antidotal treatment is not only able to protect the experimental animals from the lethal effects of tabun but also to eliminate most of tabun-induced signs of neurotoxicity in tabun-poisoned rats.

Animals↗
PubMed1976

Pharmacological approaches to treating the obese patient.

It should be obvious from the foregoing discussion that, at the present time, there is not an acceptably safe and effective pharmacological treatment for obesity. This patent inadequacy of present drug regimens has spawned the investigation into the diverse pharmacological approaches reviewed in this paper as well as investigation into the intestinal bypass operation (see Chapter 10). We feel that the eventual, safe and effective therapy for obesity will come from the pharmacological realm. Glucose-blocking drugs, growth hormone analogues, and hydroxycitrate are but three of the potentially safe and effective approaches to the problem for the future. It will be truly fascinating to watch the development in the treatment of obesity and, specifically, the pharmacological treatment for this problem over the next five to ten years.

Amphetamines↗
PubMed2002

[The efficacy of scheduled cardioversion in atrial fibrillation. Comparison of two schemes of treatment: electrical versus pharmacological cardioversion].

INTRODUCTION AND OBJECTIVES: Atrial fibrillation is an arrhythmia with high morbidity and mortality. Restoring sinus rhythm is one of the principle objectives in its management. The present study aimed to assess the efficacy of scheduled cardioversion on atrial fibrillation by comparing two different therapeutic approaches: electrical vs. pharmacological cardioversion. PATIENTS AND METHOD: Two hundred thirty patients with atrial fibrillation of more than 48 hours duration and requiring sinus rhythm restoration were included. One hundred forty-four patients underwent external electrical cardioversion and 86 patients received quinidine. We analyzed the rate of success, duration of hospital stay, complications and clinical and echocardiographic variable that might predict success. RESULTS: Sinus rhythm was restored in 181 of 230 patients (79%). The rate of success was 77% (111/144 patients) in the electrical group and 81% (70 of 86 patients) in the pharmacological group (ns). In 13 pharmacological group patients for whom the first attempt failed attempt, a second attempt with electrical cardioversion was made and was successful in 8 patients (61%). No embolic complication was recorded and only two electrical disturbances were seen. Only atrial fibrillation lasting less than 8 weeks was associated with a higher success rate (p < 0.01). CONCLUSIONS: Scheduled cardioversion in atrial fibrillation is an effective technique with a high success rate and a very low rate of complication. Electrical cardioversion and pharmacological cardioversion with quinidine are similarly effective, although the latter involves a longer hospital stay.

Atrial Fibrillation↗
PubMed2001

Update in pharmacologic treatment of hypertension.

Initial pharmacologic therapy for hypertension is low-dose thiazide diuretics, beta-blockers, and ACE inhibitors. Increasing data have confirmed that ACE inhibitors have specific benefit in patients with diabetes, atherosclerosis, left ventricular dysfunction, and renal insufficiency. CCBs are alternative agents for ISH in the elderly and appear to decrease stroke with perhaps less protection against progression of renal insufficiency and proteinuria, CAD mortality and new onset heart failure versus other initial agents, especially ACE inhibitors. ARBs are well tolerated and effective blood pressure lowering agents but have not been confirmed as effective as ACE inhibitors for reducing renal progression, clinical events, or mortality from heart failure. Effective pharmacologic antihypertensive therapy may avoid disabling and undetected cerebrovascular disease, cognitive dysfunction, and disturbing symptoms of elevated blood pressure. Vasopeptidase inhibitor, such as omapatrilat, and endothelin-1 antagonist, such as bosentan, may become future agents approved for the reduction of morbidity and mortality with hypertension. The ALLHAT trial continues to examine the potential benefits and harms of amlodipine versus chlorthalidone and lisinopril in a diverse high-risk population. Based on ALLHAT data, however, doxazosin is no longer an acceptable initial pharmacological agent. Intensive pharmacologic treatment with blood pressure lowering to less than 130/85 mm Hg is recommended with diabetes, renal insufficiency, and heart failure with additional goal of less than 125/75 mm Hg with renal failure and proteinuria greater than 1 g/24 h, based on multiple outcome studies.

Adrenergic beta-Antagonists↗
PubMed1999

Pharmacologic considerations in the treatment of neonatal septicemia and its complications.

This article focuses on the pharmacologic properties of drugs commonly used in the treatment of neonatal septicemia and its complications. Rational therapy demands an awareness of not only the pharmacology of individual drugs but also the interactions and anticipated fate of such drugs in the rapidly changing physiologic environment of the neonate. Further research in the area of equine neonatal pharmacology should greatly assist our understanding of the impact of the disease state on the unique physiology of the newborn and should allow us to better predict the ultimate fate of drugs commonly used for such purposes. Careful dosing and close monitoring of pharmacologic effects are critical for a successful outcome. In the future, newer therapeutic strategies that are safe and efficacious may provide a means to circumvent many of the problems currently encountered with treating the septicemic newborn foal.

Animals↗
PubMed1997

Non-pharmacological therapies in osteoarthritis.

Non-pharmacological therapies are very important in osteoarthritis. Each form of this treatment should be individually devised, taking into account the anatomical distribution, the phase and the progression rate of the disease. Indications, contraindications, dosage and precautions are as important in non-pharmacological therapy as they are in drug treatment. Therapeutic exercises decrease pain, increase muscle strength and range of joint motion as well as improve endurance and aerobic capacity. Exercise programmes should be designed, conducted and regularly supervised by professionally trained physiotherapists. Weight reduction is of proven benefit in obese patients with osteoarthritis of the knee. Walking aids, crutches, shoe insoles, braces and patellar taping are useful tools in some form of osteoarthritis. Patient education and the management of the psychosocial consequences are priority tasks. Therapeutic heat and cold, electrotherapy, ultrasound, acupuncture, hydrotherapy and spa treatment are widely used, although the effects and benefits have not been fully established. Non-pharmacological therapies should undergo rigorous randomized controlled trials in a similar manner to pharmacological studies.

Aged↗
PubMed1997

Pharmacology of neuronal nicotinic acetylcholine receptor subtypes.

The search for the physiological function of nicotinic receptors on neurons in the brain began with their discovery. It was initially assumed that, as in ganglia and at the neuromuscular junction, nicotinic receptors would gate fast synaptic transmission in the brain. The best functional evidence now, however, points to a role in modifying the release of other transmitters. This does not preclude a postsynaptic role in transmission for nicotinic receptors in the brain, but attempts to locate such a synapse have not been successful. If fast nicotinic synapses are present in the brain, they are probably low in number and may be masked by other more prevalent synapses (such as glutamatergic) so identification will not be easy. The extent of diversity of nicotinic receptors is substantial. At the molecular level this is reflected in the number of different genes that encode receptor subunits and the multiple possible combinations of subunits that function in expression systems. From the cellular level there is a broad diversity of properties of native receptors in neurons. Some useful pharmacological tools allow the limited identification of subunits in native receptors. For example, block by alpha-bungarotoxin identifies alpha 7, alpha 8, or alpha 9 subunits; activation of a receptor by cytisine indicates an alpha 7 or beta 4 subunit; and neuronal bungarotoxin block identifies a beta 2 subunit. Despite the clues to identity gained by careful use of these agents, we have not been able to identify all the components of any native receptor based on pharmacological properties assessed from expression studies. When both pharmacological and biophysical properties of a receptor are taken into consideration, none of the combinations tested in oocytes mimics native receptors exactly. The reason for this discrepancy has been debated at length; it is possible that oocytes do not faithfully manufacture neuronal nicotinic receptors. For example, they may not correctly modify the protein after translation or they may allow a combination of subunits that do not occur in vivo. Another possibility is that correct combinations of subunits have not yet been tested in oocytes. Data from immunoprecipitation experiments suggest that many receptors contain three or more different subunits. Results from further experiments injecting combinations of three or more subunits into oocytes may be enlightening. The diversity of receptors may allow targeting of subtypes to specific locations. Nicotinic receptors are located presynaptically, preterminally, and on the cell soma. The function of the nicotinic receptors located on innervating axons is presumably to modify the release of other neurotransmitters. It is an attractive hypothesis that nicotinic receptors might be involved in modifying the weight of central synapses; however, in none of the regions where this phenomenon has been described is there any evidence for axoaxonal contacts. The presynaptic receptors described so far are pharmacologically unique; therefore, if there are different subtypes of nicotinic receptors modifying the release of different transmitters, they may provide a means of exogenously modifying the release of a particular transmitter with drugs. There are still many basic unanswered questions about nicotinic receptors in the brain. What are the compositions of native nicotinic receptors? What is their purpose on neurons? Although there is clearly a role presynaptically, what is the function of those located on the soma? Neuronal nicotinic receptors are highly permeable to calcium, unlike muscle nicotinic receptors, and this may have important implications for roles in synaptic plasticity and development. Finally, why is there such diversity? (ABSTRACT TRANCATED)

Animals↗
PubMed1997

The pharmacology of (-)-nicotine and novel cholinergic channel modulators.

Advances in the understanding of the molecular biology and pharmacology of nAChRs may provide targets for the development of novel and selective modulators of nAChRs in the brain. This contention is supported by the dissimilar behavioral effects observed following systemic administration of currently available nicotinic ligands. The concept of multiple subtypes of nAChRs is not unique, as evidenced by the pharmacology of other ligand-gated ion channels, such as GABA-A receptor, which also exist in multiple subtypes. At present, with respect to the nAChRs, relatively few of the subtypes identified have been cloned from human tissue and pharmacologically evaluated, but several groups are focusing their research efforts in this direction. With a thorough understanding of the pharmacological and functional characteristics of more of the putative human nAChR subtypes, this knowledge will facilitate the discovery of more efficacious and less toxic ChCMs that may provide potential novel therapeutic agents for a variety of CNS conditions.

Animals↗
PubMed1999

Pharmacologic evaluation of isometric contraction-relaxation coupling indexes in rabbit ventricular muscle.

Investigations of the coupling between contraction and relaxation (contraction-relaxation [CRC] process) in isometric conditions are essential in determining whether pharmacologic interventions or cardiac diseases specifically modify isometric relaxation (intrinsic lusitropic effect) or change it in proportion with the accompanying changes in contractility (or inotropy). For this purpose, the CRC process is quantified by various indexes, derived from differentiation and/or curve fitting the whole or relaxation phase of the isometric twitch, one of the most used being tau, the time constant of the final iso(volu)metric phase of relaxation. Nevertheless, the possible redundancy and validity of such indexes have not been thoroughly investigated. Accordingly, we performed a pharmacologic evaluation of such indexes in isolated rabbit ventricular muscles isometrically contracting in vitro, using modifiers of either intracellular Ca(2)+ handling (nifedipine, ryanodine, 2,5-di-tert-butyl-benzohydroquinone, all negative inotropic compounds, and BAY K 8644, a positive inotropic drug), or myofibrillar Ca(2)+ sensitivity (CGP 48506, a Ca(2)+ sensitizer, and butanedione monoxime, a Ca(2)+ desensitizer, respectively positive and negative inotropic compounds). The isometric twitch in control conditions and in the presence of increasing concentration of each compound was analyzed to determine the classically used CRC and/or lusitropic indexes, derived either from single parameters such as the maximal rate or contraction and relaxation (+dT(max) and -dT(max), respectively), or from curve fitting of the whole, or part, of the twitch. As the rate of isometric relaxation is dependent on myofilament properties, we expected that compounds modifying myofibrillar Ca(2)+ sensitivity in an opposite direction (CGP 48506 vs butanedione monoxime) would be the only drugs exerting an intrinsic lusitropic and opposite effect on a validated CRC index. Results showed that (1) none of the tested compounds affected the slope of the linear relationship between peak twitch tension and dT(max), a previously assumed CRC index, sensitive only to myofibrillar Ca(2)+ sensitivity modifiers; (2) the lusitropic parameter B, derived from mathematical curve fitting of the whole isometric twitch, and the ratio +dT(max)/dT(max), exhibited similar drug- and dose-dependency, but no opposite sensitivity to CGP 48506 and BDM for either index; and (3) negative inotropic compounds dose-dependently slowed relaxation (and conversely for positive inotropes), whether the latter was quantified by the rate constant beta, derived from double exponential curve fitting of the whole relaxation phase, or by the time constants tau(L) and tau(E), derived from the curve fitting (logistic and monoexponential, respectively) of the final phase of relaxation. Nevertheless, the pharmacologicly induced changes in beta were statistically significant at lower concentrations and exhibited less individual variability, compared with the time constants. We demonstrate that intrinsic lusitropic changes can be quantified by the value of the slope of the relationship relating beta to peak isometric tension: the slope value was unchanged by Ca(2)+ handling modifiers, decreased by CGP 48506, and reversed by BDM (indicating number, negative, and positive intrinsic lusitropic effects respectively). Based on these data, we propose that the linear relationship between beta and peak isometric tension could be used a new method to assess whether pharmacologic interventions or cardiac diseases exert intrinsic effects on isometric relaxation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Pharmacologic therapy of portal hypertension and variceal hemorrhage.

Patients with large esophageal varices who are deemed compliant and have no contraindications to beta-blocker therapy should be started on nonselective beta-adrenergic blockers (Fig. 5). The dose should be titrated to a 25% decrease in resting heart rate, a resting heart rate of 55 to 60 beats per minute, or development of symptoms, in which case the dose should be decreased until the patient's symptoms abate. If available, measurements of the HVPG at baseline and 3 months can be very helpful in ascertaining the response to treatment and in making the appropriate adjustments (e.g., adding a second drug). Sclerotherapy or endoscopic variceal ligation are the preferred therapies for treatment of acute esophageal variceal bleeding. Concomitant use of vasoactive drugs can supplement endoscopic treatment. They offer the advantage of early administration as soon as the diagnosis is suspected while awaiting endoscopy. Unlike endoscopic treatment, they decrease portal pressure and are the only established treatment for nonvariceal sources of bleeding related to portal hypertension. Once the index bleed is controlled, the patient should be started on treatment to reduce the high risk of recurrent variceal hemorrhage (Fig. 6). For patients with well-compensated cirrhosis, pharmacologic therapy may be desirable. For less compliant patients or patients with decompensated cirrhosis, an endoscopic technique, such as variceal ligation, may be preferable. Combinations of pharmacologic agents or pharmacologic agents and endoscopic procedures may offer hope for better control, but their efficacy needs to be demonstrated in RCTs. For patients who rebleed despite maximal pharmacologic or endoscopic therapy, a TIPS procedure, surgically created shunt, or liver transplantation should be considered, with the decision based on the patient's condition and the local availability of these options.

Esophageal and Gastric Varices↗
PubMed1995

Non-pharmacological aspects of acute pain management.

In this paper, non-pharmacological aspects of acute pain management were explored. Much of the research to date with regard to pain management, has been done, addressing the needs of chronic rather than acute pain. It is thought that misconceptions are still held by some health care professionals regarding the adequacy of pharmacology to deal totally with the problems of acute pain management, and it is of more importance to concentrate on issues associated with chronic pain. This is borne out by the relative attention paid to acute and chronic pain in the current body of research. Some aspects of non-pharmacological methods of pain management have been well researched over the last 20 to 30 years, whilst others are more recent innovations. Non-pharmacological aspects of acute pain management were examined under two headings: 1. Psychological approaches: including preoperative information giving, cognitive methods, relaxation training, distraction, guided imagery, humour, hypnosis, music and biofeedback. 2. Complementary therapies and other techniques: including both hands on and other physical therapies using equipment: massage, aromatherapy, reflex zone therapy, acupuncture, shiatsu, therapeutic touch and TENS. There is a sound body of knowledge to support the use of many of the established nonpharmacological methods in the management of acute pain. These include: appropriate preoperative information giving, preoperative relaxation, guided imagery and breathing training, cognitive reframing, distraction in both visual and auditory (music) forms, massage, acupuncture, TENS. Other methods which may be of assistance in acute pain management but are inconclusive in their effect from the current body of available research and may require further examination include: hypnosis, humour therapy, biofeedback techniques, aromatherapy, reflex zone therapy, shiatsu, Therapeutic Touch.

Acute Disease↗
PubMed2001

Effects of chemical modifications of crotoxin B, the phospholipase A(2) subunit of crotoxin from Crotalus durissus terrificus snake venom, on its enzymatic and pharmacological activities.

Crotoxin B, the basic Asp49-PLA(2) subunit from crotoxin, the main component of Crotalus durissus terrificus venom, displays myotoxic, edema-inducing, bactericidal (upon Escherichia coli), liposomal-disrupting and anticoagulant activities. Chemical modifications of His (with 4-bromophenacyl bromide, BPB), Tyr (with 2-nitrobenzenesulphonyl fluoride, NBSF), Trp (with o-nitrophenylsulphenyl chloride, NPSC) and Lys (with acetic anhydride) residues of this protein, in addition to cleavage with cyanogen bromide (CNBr) and inhibition with ethylenediaminetetraacetic acid (EDTA), were carried out in order to study their effects on enzymatic and pharmacological activities. Lethality was reduced after modification of His or Lys residues, as well as after cleavage with CNBr, while enzymatic activity was completely abolished after modification of His or incubation with EDTA. Modification of Lys or Tyr, or cleavage with CNBr, partially reduced enzymatic activity. Anticoagulant activity was modified similarly to enzymatic activity, evidencing the dependency of this pharmacological effect on catalytic activity. Myotoxicity was reduced after modification of His or Lys, as well as after cleavage with CNBr, whereas EDTA reduced this effect to a lesser extent. Bactericidal effect was significantly reduced only after modification of Lys and after cleavage with CNBr. Edema-inducing activity was partially inhibited after treatment with EDTA and strongly reduced after acetylation of Lys residues and cleavage with CNBr, being only partially reduced after His alkylation. On the other hand, liposome disrupting activity was only partially reduced after modification of His and Tyr or after cleavage with CNBr. Modification of Trp residue partially reduced lethality and myotoxicity but did not affect enzymatic or anticoagulant activities. These data indicate that enzymatic activity is relevant for some pharmacological effects induced by crotoxin B (mainly lethal, myotoxic and anticoagulant activities), and also evidence that this subunit of crotoxin displays regions different from the active catalytic site which are involved in some of the toxic and pharmacological effects induced by this phospholipase A(2).

Amino Acid Sequence↗