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PubMed1996

Predictability of the clinical potency of NSAIDs from the preclinical pharmacodynamics in rats.

OBJECTIVE AND DESIGN: Relevance of the preclinical pharmacodynamic, toxicity and pharmacokinetic parameters predicting the clinical potency of nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated. MATERIAL: Data for oral potencies of 24 NSAIDs in rats were collected from the literature and from New Drug Applications with respect to the following parameters: antiinflammatory, analgesic, antipyretic, acute ulcerogenic activities, acute toxicity, in vitro inhibition of prostaglandin synthesis, acid dissociation constant (pKa), octanol-water partition coefficient and elimination half-life. TREATMENT: Data for most of the in vivo parameters in rats were collected following single dose administration with the exception of adjuvant arthritis. Single and daily clinical doses were considered. All of these NSAIDs have been approved for marketing although not all have been sold in the USA. METHODS: The preclinical data were compared to human dose (unit or daily doses) using single and multiple stepwise regression analyses. RESULTS: Analyses suggest that NSAIDs are effective in all models of preclinical tests for fever, pain and inflammation, however, carrageenin-induced rat paw edema model is clearly the best predictor of human dose. Rank order of preclinical models for predicting human dose is carrageenin > yeast induced fever > pressure induced pain = adjuvant arthritis in rats. The analysis suggested that the pain and adjuvant arthritis models in rats may also involve a prostaglandin independent mechanism. Of the two physicochemical factors tested, pKa contributed best to the carrageenin model towards predicting the clinical potency of NSAIDs. Mathematical relationships between human dose, carrageenin ED50 and pKa were established that may assist in the future clinical development of NSAIDs. CONCLUSIONS: Carrageenin-induced paw edema model in rats is the most robust predictor of the clinical potency of NSAIDs. Acid dissociation constant (pKa) appears to be a secondary contributor to the potency of NSAIDs. The relevance of the data analyses for developing cyclooxygenase-2 (COX-2) selective NSAIDs is discussed.

Administration, Oral↗

PubMedDate not supplied

Chronopharmacokinetics of acetaminophen in healthy human volunteers.

Acetaminophen is a common antipyretic-analgesic drug usually administered orally any time of the day. It was however claimed by Belanger et al, (1985) to have a longer elimination half-life (t1/2 beta) in rats when administered by 2100 h, than at 0700 h. This work is designed to investigate this claim in man and to study the circadian changes in acetaminophen pharmacokinetics at three dosing times; 0730 h, 1300 h and 2100 h. Seven healthy male volunteers, age 26.28 +/- 3.01 years, weighing 65.00 +/- 2.2 kg, were administered with 1000 mg oral acetaminophen at the three circadian time after a period of fast of not less than 4 h. The pharmacokinetic values obtained, though varied, are found to be in similar ranges with previously reported values. The absorption parameters ka and mean Tmax were significantly altered with dosing at 0730 h and 2100 h while the mean t1/2 alpha and ka were also significantly changed. There was a significant difference (P < 0.05) between the Tmax values obtained at 2100 h and that of 0730 h, while the 34.9% increase at dosing time 1300 h over 0730 h dosing times is not statistically significant (P > 0.05). Cmax was found to be 22.31 +/- 4.24 mcg/ml for 0730 h dosing time, while a decrease of 9.64 and 11.7% over this value was recorded for dosing time 1300 h and 2100 h respectively. The changes are however not statistically significant (P > 0.05). AUCo-a at 0730 h did not show any significant change when compared with values obtained at 1300 h and 2100 h, but there was a significant difference between the values obtained at 1300 h and 2100 h. Elimination half-life, t1/2 beta was found to be 1.68 +/- 0.67 h at 0730 h. There was an increase of 13.1% and 20.83% over this value at 1300 h and 2100 h. These increases were not statistically significant (p > 0.05). Although there are similar increases in t1/2 beta at the 1300 h and 2100 h dosing time as reported by Belanger et al 1985, the increases were not statistically significant in man.

Acetaminophen↗

PubMedDate not supplied

Effect of zobo drink (Hibiscus sabdariffa water extract) on the pharmacokinetics of acetaminophen in human volunteers.

Acetaminophen, a common antipyretic-analgesic OTC drug is often administered orally anytime of the day with water or beverages irrespective of possible interactions. Zobo drink, is a sweetened water extract of the dried calyx of Hibiscus Sabdariffa. This work is designed to investigate the effect of zobo drink on an oral dose of acetaminophen. Six healthy male volunteers, ages 28.50 +/- 1.76 years, weighing 62.67 +/- 1.67kg participated in the study. The study was carried out in two phases. In the first phases an oral dose of acetaminophen (1g) was administered to the volunteers and in the second phases, zobo drink was ingested by the volunteers 1.30 h prior the administration of acetaminophen (1g). Acetaminophen concentration in plasma was determined using a validated spectrophotometric method. Pharmacokinetic values obtained were found to be in similar ranges as those previously reported. The absorption parameters t1/2a, Ka, Tmax, Cmax and AUC0-alpha showed no statistically significant changes (p>0.05) after the administration of zobo. There were however statistically significant changes (p<0.05) in Kbeta and t1/2beta of acetaminophen when administered after the zobo drink. This also resulted in 11.69% increase in ClT.

Acetaminophen↗

PubMed2003

Inflammatory mediators do not stimulate CGRP release if prostaglandin synthesis is blocked by S(+)-flurbiprofen in isolated rat skin.

OBJECTIVE: Nonsteroidal antiinflammatory drugs are well known as antipyretic analgesics, however, their mode of action is not yet fully understood. Besides their cyclooxygenase (COX) blocking effect other action principles are discussed. In the present study we investigated the effects of the flurbiprofen enantiomers on the stimulated release of calcitonin gene-related peptide (CGRP) from the isolated rat skin as an indirect measure of peripheral nociceptor activation and 'neurogenic inflammation'. METHODS: Stimulation was performed by a combination of inflammatory mediators (bradykinin, serotonin and histamine, all 10(-5) M). In addition, prostaglandin E(2) (PGE(2)) release was determined in order to verify the inhibitory effect of the tested drugs on prostaglandin production. RESULTS: S(+)-flurbiprofen (10(-7) and 10(-6) M), reported as the COX blocking enantiomer, completely blocked basal as well as stimulated PGE(2) release. Under R(-)-flurbiprofen a reduction of basal PGE(2) release was not significant; the stimulated PGE(2) release, was however significantly reduced at 10(-7) M and completely suppressed at 10(-6) M drug concentration. The stimulated CGRP release was not affected by R(-)-flurbiprofen (10(-7) or 10(-6) M). In contrast, S(+)-flurbiprofen - only at 10(-6) M - significantly reduced the inflammatory mediator-induced CGRP release. This reduction could be reversed by co-administration of PGE(2) (10(-5) M) suggesting that the effect was due to COX block and prostanoid deprivation. CONCLUSION: Although a higher concentration of the effective enantiomer was needed to inhibit stimulated CGRP than PGE(2) release, flurbiprofen seems to exert the antinociceptive/antiinflammatory effects observed by preventing the secondary cutaneous prostaglandin formation that appears necessary to enable activation by inflammatory mediators of the CGRP-releasing nerve fibers.

Animals↗

PubMed2001

Pharmaceutically relevant metabolites from lichens.

Lichen metabolites exert a wide variety of biological actions including antibiotic, antimycobacterial, antiviral, antiinflammatory, analgesic, antipyretic, antiproliferative and cytotoxic effects. Even though these manifold activities of lichen metabolites have now been recognized, their therapeutic potential has not yet been fully explored and thus remains pharmaceutically unexploited. In this mini-review, particular attention is paid to the most common classes of small-molecule constituents of lichens, from both the chemical viewpoint and with regard to possible therapeutic implications. In particular, aliphatic acids, pulvinic acid derivatives, depsides and depsidones, dibenzofuans, anthraquinones, naphthoquinones as well as epidithiopiperazinediones are described. An improved access to these lichen substances in drug discovery high-throughput screening programs will provide impetus for identifying novel lead-compounds with therapeutic potential and poses new challenges for medicinal chemistry.

4-Butyrolactone↗

PubMed1998

[2-Arylpropionic acids. Role in pain therapy].

The antipyretic analgesics still comprise the most widely used group of analgesic compounds. Until twenty years ago, aspirin, phenazone derivatives and acetaminophen had been used as standard remedies for intercurrent harmless pain conditions in connection with infections, trauma, small surgeries, but also for tension headache and other painful conditions. During the last decades, this group has been supplemented by a variety of 2-arylpropionic acids being primarily developed for the treatment of rheumatic pain and inflammation. Some of them (e.g. ibuprofen, ketoprofen and naproxen) have been given over-the-counter status in some countries because of their relative safety at low doses. Nevertheless, pharmacodynamic and pharmacokinetic differences among the various substances of this group make them suitable to a different degree for the treatment of pain conditions.

English Abstract↗

PubMed2002

Pharmacoeconomic analysis of prescriptions in Italian pediatric general practice.

Most drugs used by children are prescribed by general pediatric practitioners (GPPs) in ambulatory settings. Prescription profiles are affected by GPPs' attitudes while the cost is related to the reimbursement modality. This study evaluated the Italian National Health Service (INHS) and family expenditures associated with prescribing practices to children younger than 12 years. Forty-two GPPs from southern Italy participated in the study. All visits recorded by GPPs during a 13-week period (February-April 1998), including telephone contacts and office and home visits were analyzed. The cost analysis of prescriptions is based on a sample of randomly selected consultations. INHS and family expenditures were evaluated according to reimbursement modalities for drug prescriptions. Total expenditure induced by all prescriptions during the study period was about 148 million Italian lire (7650 euros); 54% of this was borne by the INHS and the rest remaining by families. When corrections according to prescription modalities - following appropriate reimbursement form - were applied, only 49% of total expenditure were covered by INHS and 51% by families. Analysis of expenditures showed that drugs for symptomatic therapies (e.g., cough and cold preparations, analgesics, antipyretics) and vitamins accounted for most of the families' expenditure, while antibacterial and antiasthmatic drugs did so for the INHS. Of the ten most prescribed drugs the cost of three fell entirely on the family: paracetamol (the most commonly prescribed drug),morniflumate, and ambroxol. Therapeutic indications causing greatest expenditures for families were all the common,trivial childhood symptoms such as cough, fever, rhinitis, flu, and pharyngitis. Despite the universal coverage for pharmaceutical care more than one-half of drug therapy expenditures for children was covered directly by the parents. Prescription attitudes by GPPs remain the crucial factor for an equal cost distribution between families and the INHS.

Journal Article↗

PubMed1983

The biologic background to some therapeutic uses of aspirin.

The therapeutic success of aspirin as an effective analgesic, antipyretic, and anti-inflammatory drug had been universally established for many decades before its mode of action was discovered in 1971. This mode of action is the prevention, or diminution, of prostaglandin biosynthesis through the inhibition of the enzyme, cyclo-oxygenase. Demonstrations of the major contributions of prostaglandins to pain, fever, and other cardinal features of inflammation provided rational explanations for the well-established therapeutic uses of aspirin. It had been shown earlier that aspirin antagonized two mediators of inflammation by an indirect process. While aspirin's mode of action was being discovered, research on platelets in hemostasis and thrombosis was also being done. It was shown that aspirin inhibited an exocytotic reaction (the release reaction) of platelets. This reaction was regarded as essential for their aggregation as thrombi in, most importantly, coronary and cerebral arteries. This observation was the starting point of an enormous effort, still going on to determine through both fundamental and clinical investigations, the therapeutic potential of aspirin as an antithrombotic drug. Costly clinical trials have provided evidence in favor of aspirin preventing thrombotic events affecting the brain; its effectiveness against coronary thrombosis is not yet definitely established. Possible explanations for this situation will be considered on the basis of rapidly advancing biologic knowledge about the mechanism of thrombosis.

Animals↗

PubMed1988

Role of disease-modifying antirheumatic drugs versus cytotoxic agents in the therapy of rheumatoid arthritis.

Disease-modifying antirheumatic drugs are used to modify or alter the rheumatoid arthritis disease process. Disease-modifying antirheumatic drugs do not demonstrate the characteristic analgesic, antipyretic, and anti-inflammatory actions of the nonsteroidal anti-inflammatory drugs, since weeks or months of treatment are required before clinical benefit is observed. Although they have not been proved to delay, prevent, or reverse articular damage, therapy with disease-modifying antirheumatic drugs, when successful, is associated with decreased pain and joint swelling and improved function. Disease-modifying antirheumatic drugs and cytotoxic agents should not be considered as routine treatment for patients with rheumatoid arthritis. Before disease-modifying antirheumatic drug therapy is implemented, an optimal basic program of physical therapy, rest, and nonsteroidal anti-inflammatory drugs should be implemented, and it must be documented that the patient still has sufficient disease to justify the costs, risks, and benefits of these treatments. Drugs that are approved by the Food and Drug Administration (FDA) are preferred over nonapproved drugs. Hydroxychloroquine, parenteral gold salts, oral gold, D-penicillamine, and the cytotoxic drug azathioprine are the FDA-approved disease-modifying antirheumatic drugs for use in rheumatoid arthritis. Many, not all, rheumatologists would employ hydroxychloroquine as the first-choice disease-modifying antirheumatic drug in patients who have early, mild, and nonerosive disease; treatment should be continued for six months before being abandoned for lack of efficacy, and appropriate ophthalmologic examination every four to six months is indicated. An alternative would be auranofin, whose efficacy approaches that of parenteral gold, yet may be safer. For patients who have severe active rheumatoid arthritis, especially with erosive changes, parenteral gold salts are usually a first choice. D-penicillamine is also effective in controlling the signs and symptoms of rheumatoid arthritis, but serious toxicity may occur. Azathioprine might be considered a competitor to D-penicillamine, although the FDA approval restricts its use to patients who have failed gold therapy. Two cytotoxic drugs that are not FDA approved are methotrexate and cyclophosphamide. Methotrexate can be very effective, but its side effects, particularly pulmonary and hepatic, must be carefully monitored. Cyclophosphamide is generally considered too toxic for use in patients with rheumatoid arthritis, although it may be helpful in patients with systemic rheumatoid vasculitis or patients who have failed all other therapies.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Inflammatory Agents↗

PubMed1995

Dipyrone metabolism in liver disease.

BACKGROUND AND OBJECTIVES: Dipyrone is an analgesic, antipyretic, and anti-inflammatory drug. After oral administration it is hydrolyzed to 4-methylaminoantipyrine and further metabolized to 4-aminoantipyrine, 4-formylaminoantipyrine, and 4-acetylaminoantipyrine. This study investigated the disposition of dipyrone metabolites in 12 hospitalized patients with cirrhosis (age, 25 to 65 years) and 27 healthy subjects of two age groups (young, 21 to 40 years; elderly, 73 to 90 years). METHODS: Subjects received 1 gm dipyrone orally, and blood samples were drawn and urine collected over 72 hours. Plasma and urine concentrations of the four metabolites were determined by HPLC. RESULTS: 4-Methylaminoantipyrine terminal elimination half-life (t1/2 beta) in patients with cirrhosis was prolonged compared with young and elderly subjects (mean +/- SEM, 10.6 +/- 0.6 versus 3.1 +/- 0.2 and 4.9 +/- 0.6 hours, p < 0.001), and the nonrenal clearance was reduced compared with the young subjects (1.069 +/- 0.243 versus 2.165 +/- 0.154 ml/min/kg, p < 0.005). 4-Formylaminoantipyrine was undetectable in two patients and in the remaining 10 patients, t1/2 was longer than in the young subjects (26.4 +/- 4.3 versus 10.8 +/- 0.7 hour, p < 0.01), whereas the elderly had intermediate values (18.1 +/- 2.8 hours). Clearance for production of 4-formylaminoantipyrine was reduced in the patients with cirrhosis than in the young and elderly subjects (0.109 +/- 0.024 versus 0.363 +/- 0.031 and 0.340 +/- 0.053 ml/min/kg, p < 0.001). The acetylation phenotype was determined to evaluate the pharmacokinetic parameters of 4-aminoantipyrine and 4-acetylaminoantipyrine. Prolongation of the 4-aminoantipyrine t1/2 and decrease in its clearance for production was found for the patients with cirrhosis, both slow and rapid acetylators, compared with the young and elderly subjects (p < 0.01). 4-Acetylaminoantipyrine t1/2 was also prolonged for patients with cirrhosis, slow and rapid acetylators, compared with the young subjects (p < 0.005). In the slow acetylators, clearance for production of 4-acetylaminoantipyrine did not differ between the patients with cirrhosis and the young subjects (p < 0.5); however, a difference was found for the rapid acetylators (p < 0.001). CONCLUSION: Our results show that the disposition of 4-methylaminoantipyrine, 4-aminoantipyrine, 4-formylaminoantipyrine, and 4-acetylaminoantipyrine is reduced by chronic liver disease after a single oral dose of dipyrone.

Acetylation↗

PubMed1992

The pharmacological differences and similarities between stress- and ethanol-induced gastric mucosal damage.

Stress- and ethanol-induced gastric mucosal damage are the two commonly used ulcer models in animals. They share some of the similarities but also have differences in the etiology of gastric ulceration. This article reviews the influences of various protective drugs on these two types of gastric damage in rats. Verapamil (a calcium antagonist) or N-ethylmaleimide (a sulfhydryl depletor) prevents cold restraint-, but potentiates ethanol-provoked gastric lesion formation. N-Acetylcysteine (a mucolytic agent) and acetaminophen (an antipyretic analgesic) have the opposite actions. Prostaglandins provide a much better antiulcer effect on ethanol-induced lesions. Cimetidine (a histamine H2-receptor antagonist) prevents only stress-induced mucosal damage. These differences in drug actions indicate that stress and ethanol may have dissimilar ulcerogenic mechanisms in rats. On the other hand, carbenoxolone (a mucus inducer), histamine H1-receptor antagonists, leukotriene inhibitors (FPL 55712 and nordihydroguaiaretic acid) and mast cell stabilizers (like zinc compounds, sodium cromoglycate, FPL 52694 and ketotifen), all protect against gastric mucosal damage by stress or ethanol in rats. However, the role of gastric sulfhydryls in both types of gastric lesions is still controversial. These findings imply that the two types of lesion formation share some of the ulcerogenic mechanisms. This communication attempts to analyze the various findings and to relate them to the etiology of stress and ethanol-induced gastric lesions. It also summarizes the uses, and the antiulcer mechanisms, of the drugs that have been studied utilizing these two animal ulcer models, and suggests their possible implications in man.

Acetaminophen↗

PubMed1995

Neuronal expression of FOS protein in the nucleus tractus solitarii and the dorsal motor nucleus of the vagus nerve after i.p. injection of ulcerogenic aspirin.

Aspirin, a common analgesic-antipyretic and anti-inflammatory drug, often induces gastric ulcer, but its pathogenesis remains unsettled. The purpose of this study was to identify the CNS neurons that express FOS protein after i.p. injection of aspirin (100-300 mg/kg). This was done in the unanesthetized Wistar rats with careful physiological controls. Dose-dependently, many FOS-immunoreactive (FOS-ir) neurons were found in the medial part of the nucleus tractus solitarii (NTSm) and the dorsal motor nucleus of the vagus nerve (DMX) of the lower medulla, but none in the paraventricular nucleus of the hypothalamus (PVH). Distribution of FOS-ir neurons in the DMX corresponds with that of the visceromotor neurons involved in gastric secretion. This study suggests that the aspirin-induced gastric ulcer may not originate in the PVH but in the NTSm-DMX system.

Animals↗

PubMed1981

Age-associated changes of responses to acetylsalicylic acid.

Aspirin can be an effective antipyretic, analgesic and anti-inflammatory agent, but unfortunately, its use in the elderly is often excessive [43]. In a survey by Gillies and Skyring, the overall prevalence of daily aspirin intake was greater in middle-age and older-age groups than for those of less than 40 years of age [16]. The elderly are susceptible to the advertising of non-prescription drugs and aspirin is frequently self-prescribed [8,31]. Age-related physiological changes modify the response to aspirin in the elderly. A higher incidence of drug reactions and interactions has been evidenced in this age group. The cases cited throughout this report substantiate the need for caution on the part of the geriatric patient and the physician in regard to aspirin therapy for the elderly.

Age Factors↗

PubMedDate not supplied

Ethnopharmacology of Calotropis procera flowers.

An ethanolic extract of the flowers of Calotropis procera was investigated for anti-inflammatory, antipyretic, analgesic and antimicrobial activities. The plant extract reduced the paw swelling induced by carrageenan by 37%, fever in rats by 40% and showed some weak effect in rats on the writhing induced by acetic acid. The growth of both gram-positive and gram-negative bacteria was significantly inhibited. A dose-dependent effect on prostaglandin release was also observed.

Animals↗

PubMed1991

A longitudinal evaluation of drug use in an ambulatory elderly population.

Participants in a geriatric health screening program were studied longitudinally to determine the patterns of drug use over a 10 year period. There were 314 (34.0%) men and 610 (66.0%) women who completed 10 yearly health screening evaluations. The mean number of prescribed and non-prescribed drugs used per participant increased from 2.90 in 1978-79 to 4.08 in 1987-88 (p less than 0.0001). There was no significant difference between men and women in the rate of increased drug use. There was no significant increase in the mean number of drug ingredients per participant used over the 10 year period. The most frequently reported therapeutic categories for 1978-79 were antihypertensives, analgesic-antipyretics, antirheumatics, multiple vitamins, cathartics and vitamin E, which represented 10.2, 7.2, 6.5, 4.9, 4.8 and 3.8% of all categories used. There was a decline in all of these categories between interval 1 and 10. Increased use of drugs, particularly prescribed medications, by the elderly population may present problems of adverse drug reactions, drug interactions and medication compliance in the future. Changing patterns of drug use may have resulted, in part, from introduction of new therapeutic classes and from new treatment concepts over the 10 year study period.

Aged↗

PubMed2004

Hydrotropic solubilization of nimesulide for parenteral administration.

Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) that exhibits analgesic, antipyretic and anti-inflammatory activities. It is practically insoluble in water. The effect of various hydrotropes such as nicotinamide, sodium ascorbate, sodium benzoate, sodium salicylate and piperazine on the solubility of nimesulide was investigated. The solubility enhancement of nimesulide by the hydrotropes was observed in decreasing order as piperazine > sodium ascorbate > sodium salicylate > sodium benzoate > nicotinamide. In order to elucidate the probable mechanism of solubilization, various solution properties of hydrotropes such as viscosity, specific gravity, surface tension, refractive index, specific conductance of hydrotropic solutions were studied at 25 +/- 2 degrees C on the basis of earlier studies. The hydrotropic solubilization of nimesulide at lower hydrotrope concentration may be attributed to weak ionic interactions while that at higher hydrotrope concentration may be due to molecular aggregation. Parenteral formulations using piperazine as a hydrotrope were developed and studied for physical and chemical stability.

Infusions, Parenteral↗

PubMed2004

Determination of thiocyl in biological samples by liquid chromatography with ThioGlo 3 derivatization.

Thiocyl (sodium thiosalicylate) belongs to a salicylate group of drugs, thus it has analgesic, antipyretic and anti-inflammatory effects. It possesses metal chelating function because it also belongs to a thiol-containing group of compounds which are well-known chelators. The studies of our research group showed that thiocyl is a promising chelator of lead poisoning due to its antioxidant and metal-chelating abilities. To the best of our knowledge, no methods were currently available for measuring thiocyl in biological samples. Therefore, we developed a reversed-phase HPLC method using fluorescence detection (lambdaex = 365 nm, lambdaem = 445 nm) with a one-step derivatizing reaction between thiocyl and a derivatizing agent-ThioGlo 3 (9-acetoxy-2-(4-(2, 5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)pyenyl)-3-oxo-3H-naphtho[2,1-b]pyran). Most biological thiols (such as N-acetylcysteine (NAC), cysteine (CYS), glutathione (GSH) and homocysteine (HCYS)) do not interfere with the detection of thiocyl by using this technique. The linear range of its calibration curve was determined to be 25-2500 nM, and the detection limit of thiocyl was found to be 3 nM with 20 microL injection volume. The coefficients of variation (CV) for within-run precision and between-run precision ranged from 0.93 to 7.21%. This assay proved to be a rapid, sensitive and simple method for determining thiocyl in biological samples.

Benzoates↗

PubMed2005

Bacopa monniera, a reputed nootropic plant: an overview.

Bacopa monniera (BM), a traditional Ayurvedic medicine, used for centuries as a memory enhancing, anti-inflammatory, analgesic, antipyretic, sedative and antiepileptic agent. The plant, plant extract and isolated bacosides (the major active principles) have been extensively investigated in several laboratories for their neuropharmacological effects and a number of reports are available confirming their nootropic action. In addition, researchers have evaluated the anti-inflammatory, cardiotonic and other pharmacological effects of BM preparations/extracts. Therefore, in view of the important activities performed by this plant, investigation must be continued in the recently observed actions described in this paper. Moreover, other clinical studies have to be encouraged, also to evidence any side effects and possible interactions between this herbal medicine and synthetic drugs.

Animals↗