Biomedical subjects

A Filippelli

Publications and source records attributed to A Filippelli.

At least 37 records · Page 2Linked to original sources

PubMed1998

Neuronorm is a potent and water soluble neurokinin A receptor antagonist.

We report here the synthesis and preliminary pharmacological characterization of a novel water soluble Neurokinin A receptor antagonist named Neuronorm. The synthesis was achieved in high yield by a combination of classical peptide synthesis methodologies, in both solution and solid phase. The pharmacological properties as neurokinin A receptor antagonist were assessed in in vitro experiments on rat vas deferens and guinea pig trachea, and were compared to those of MEN10627.

Animals↗

PubMed1998

A novel super-potent neurokinin A receptor antagonist containing dehydroalanine.

We report here the synthesis and preliminary pharmacological characterization of a novel Neurokinin A receptor antagonist. This molecule contains a dehydroalanine residue. It displays a high conformational rigidity and possesses very high activity. Its pharmacological properties as a neurokinin A receptor antagonist were assessed in in vitro experiments on rat vas deferens and were compared to those of Neuronorm and MEN10627.

Alanine↗

PubMed1998

Research on heterocyclic compounds, Part 40. 2-Phenylimidazo[1,2-a]pyridine-3-carboxylic acid derivatives: synthesis and antiinflammatory activity.

A series of 2-phenylimidazo[1,2-a]pyridine-3-carboxylic esters, acids, and amides were synthesized and pharmacologically tested in order to evaluate their antiinflammatory and analgesic activity and their ulcerogenic action on the gastro-intestinal tract. The most active member of this series of compounds was found to be 6-methyl-2-phenylimidazo[1,2-a]pyridine-3-carboxylic acid (5c).

Animals↗

PubMed1998

Endothelin-1 and bronchial hyperresponsiveness in the rabbit.

Endothelins (ETs) are a family of peptide mediators that have a number of biological properties, including the ability to act as potent bronchoconstrictors of isolated human airways. Moreover, elevated concentrations of ET-1 in the bronchoalveolar lavage fluid from patients with symptomatic asthma have also been detected. We investigated the possible contribution of ET-1 in the development of bronchial hyperresponsiveness and the role of inflammatory cell accumulation in rabbit lungs. Our data show that ET-1 challenge to rabbits does not modify basal lung function but results in an increased airway responsiveness to inhaled histamine. Endothelin-treated rabbits were 3-fold (P<0.01) more responsive to inhaled histamine when compared with vehicle-treated rabbits. This hyperresponsiveness was not associated with an alteration in either total or differential inflammatory cell numbers as assessed by bronchoalveolar lavage (BAL). Pre-treatment with capsaicin (80 mg/kg s.c.) did not alter basal lung function or basal responsiveness to inhaled histamine. While capsaicin had no significant effect on the acute bronchoconstriction induced by endothelin-1, this dose was sufficient to significantly inhibit the increase in airway responsiveness to inhaled histamine, achieved 24 h following endothelin-1 challenge. These results indicate that ET-1 may play a role in the development of bronchial hyperresponsiveness to inhaled histamine and that the maintenance of this state is unrelated to a detectable alteration in cellular infiltration within the airway lumen, but probably via the involvement of capsaicin-sensitive nerves.

Airway Resistance↗

PubMed1998

Cardiotoxicity of doxorubicin: effects of 21-aminosteroids.

The purposes of this study were to investigate in vivo the effects of two lazaroids,U-74389G (21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-pregna-1,4,9 (11)-triene-3,20-dione (2)-2-butenenedionate) and U-83836E (-)-2-[[4-(2,6-di-1-pyrrlidinyl-4-pyrimidinyl)-1-piperazinyl]methy l]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, dihydrochloride against the cardiotoxicity induced by doxorubicin in rat and the mechanisms underlying such a toxicity. Doxorubicin (DXR) administered intraperitoneally (5 mg/kg 4 times per week for 1 week) induced significant decrease of body weight, ECG alterations and 100% mortality. The lazaroids used in this study did not protect from DXR-induced cardiotoxicity. Our results showed that the compound U-74389G delayed, but did not reduce DXR-induced mortality, and did not prevent body weight loss and ECG changes. The compound U-83836E was unable to modify any toxic effects induced by DXR. These data indicate that oxygen free radicals and the subsequent increase in intracellular calcium are only steps of DXR progressive general toxicity that leads to cardiac injury. In conclusion, we propose that the 21-aminosteroids, potent inhibitors of membrane lipid peroxidation, alone are not enough to protect from DXR toxic effects.

Animals↗

PubMed1998

The role of A3 adenosine receptors in central regulation of arterial blood pressure.

1. Pharmacological studies have suggested that A3 receptors are present on central neurons. Recently this adenosine receptor subtype has been identified in the rat and its presence in the central nervous system has been confirmed. 2. In this study we investigated the effects of acute intracerebroventricular (i.c.v.) injections of N6-2-(4-aminophenyl)-ethyladenosine (APNEA), a non-selective A3 adenosine receptor agonist, on arterial blood pressure (ABP) and heart rate (HR), after treatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective antagonist of A1 adenosine receptors. 3. Anaesthetized rats, after DPCPX (12 microg(-1) kg i.c.v.), were treated with APNEA (0.4-4 microg kg(-1) i.c.v.) resulting in a transitory and dose-dependent decrease in arterial blood pressure without a change in heart rate. APNEA also induced hypotensive responses after i.c.v. pretreatment with aminophylline, at a dose of 20 microg kg(-1). In contrast, pretreatment 48 h before, with 4 microg kg(-1) i.c.v. of pertussis toxin reduced the hypotensive effect induced by APNEA. Administration of APNEA at a higher dose (20 microg kg(-1) i.c.v.), after DPCPX, induced a decrease in ABP of -66+/-5.4 mmHg and after 3 min a decrease in heart rate of -62+/-6.0 beats min(-1). Transection of the spinal cord abolished this significant fall in ABP, but not the decrease of HR. 4. These results suggest that a population of A3-receptors is present in the CNS, whose activation induces a decrease in blood pressure with no change of heart rate.

Animals↗

PubMed1998

Effects of hyperbaric oxygen exposure on a zymosan-induced shock model.

OBJECTIVE: To evaluate the effects of hyperbaric oxygen (HBO) therapy on zymosan-induced shock in rats. Zymosan, a cell wall component of the yeast Saccharomyces cerevisiae, induces inflammation by causing the production of various cytokines and pro-inflammatory mediators. The administration of zymosan to rats represents a new experimental shock model by inducing acute peritonitis, severe hypotension, and signs of systemic illness. However, it has been recently proposed that the zymosan-induced shock, like septic shock, may be mediated by overproduction of nitric oxide. DESIGN: Experimental study. SETTING: Institute of Pharmacology and Toxicology, 2nd University of Naples, Naples, Italy. SUBJECTS: Male rats were treated with zymosan (500 mg/kg) by intraperitoneal route, with HBO (2 Absolute Atmosphere) or with zymosan and HBO (2 Absolute Atmosphere). MEASUREMENTS AND MAIN RESULTS: Peritoneal exudate, plasma, and peritoneal nitric oxide metabolites (NOx) and zymosan determined a time-dependent increase in peritoneal and plasma NOx concentrations, and peritoneal leukocytes were determined. Moreover, symptomatology was observed. The administration of zymosan caused the appearance of a severe illness in the rats characterized by ruffled fur, lethargy, conjunctivitis, diarrhea, and a significant loss of body weight. All zymosan-treated rats developed an acute peritonitis, producing turbid exudate. Zymosan determined a time-dependent increase in peritoneal, plasma NOx, and tumor necrosis factor (TNF)-alpha concentrations. Morbidity of zymosan shocked rats has been attenuated and no mortality was observed by treatment with HBO. These findings were associated with a significant reduction either of peritoneal leukocytes and exudate, or plasma and peritoneal NOx concentrations. Moreover, TNF-alpha levels were significantly reduced in animals shocked by zymosan and treated with HBO.

Animals↗

PubMed1997

Transglutaminase-synthesized spermine derivative of substance P recognizes rat portal vein neurokinin-3 receptors.

The effects of the transglutaminase-synthesized polyamine derivatives of Substance P (SP) have been further characterized by their ability to contract in vitro the rat portal vein strip (RPV), a pharmacological preparation particularly rich in NK-3 receptors. The effects of selective agonists of NK-1, NK-2 and NK-3 receptors [Sar9,Met(O(2))11]SP, beta-Ala8 NKA(4-10), and senktide respectively, were also evaluated by measuring RPV concentration-response curves. Peptide [GR-82334 (NK-1) and MEN-10,376 (NK-2)] and nonpeptide [WIN 51,708 (NK-1) and SR 142801 (NK-3)] NK receptor antagonists were used to confirm the participation of the different NK receptors to contractile response. Our results demonstrated that the spermine derivative of SP (Spm-SP), previously shown to be unable to recognize NK-1 and NK-2 receptors in some bioassays, contracts RPV (EC50 = 588 nM) better than the native neuropeptide (EC50 = 1120 nM). A pretreatment with thiorphan, an inhibitor of neutral endopeptidases, significantly reduced such a difference. While this inhibitor shifts the SP concentration-response curves to the left (EC50 = 720 nM) the action of Spm-SP and [Sar9,Met(O(2))11]SP were completely thiorphan-resistant. In the absence of thiorphan we found the following rank order of potency: senktide > > beta-Ala8 NKA(4-10) > [Sar9,Met(O(2))11]SP = Spm-SP > SP. Among the mentioned NK receptor antagonists, only the selective NK-3 receptor antagonist, SR 142801, shifted to the right Spm-SP and [Sar9,Met(O(2))11]SP concentration-response curve, showing pKB values of 5.84 and 5.88, respectively. Therefore, the reported results suggest that the introduction of a Spm moiety into the SP alters the parent peptide molecule by increasing its affinity for NK-3 receptors and/or by preventing its degradation by some proteolytic enzymes.

Androstanes↗

PubMed1997

Role of nitric oxide in a nonseptic shock model induced by zymosan in the rat.

Nitric oxide (NO) is a short-lived mediator, the synthesis of which is induced by various cytokines during inflammatory processes. Recently, it has been proposed that zymosan, a nonbacterial agent, causes inflammation by inducing the production of various cytokines and proinflammatory mediators. In the present study we investigated the role of NO in a nonseptic shock model induced by zymosan administration in the rat. Administration of zymosan (500 mg/kg, intraperitoneally) in the rat induced acute peritonitis, as assessed by a marked increase in the leukocytes count in the exudate, as well as by an increase in the exudate nitrate/nitrite concentration. Zymosan-treated rats developed a severe hypotension and showed signs of systemic illness, significant loss of body weight, and a high mortality rate (53% of animals died within 72 h). Elevated plasma levels of nitrite and nitrate were also observed in zymosan-treated rats compared with control rats (67 +/- 4 microM and 23 +/- 2 microM, respectively; p < .01). In ex vivo experiments, vascular reactivity was studied in thoracic aorta rings of zymosan-treated rats. The contractile responses to norepinephrine (100 nM) and endothelin-1 (5 nM) were significantly reduced. An impairment of the endothelial-dependent relaxation in response to acetylcholine was also observed. Pretreatment of zymosan-shocked rats with NG-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMA), (10 mg/kg, subcutaneously, 15 min before zymosan) decreased mortality, prevented the development of peritonitis, improved ex vivo vascular reactivity, and significantly reduced hypotension. Our data suggest that overproduction of NO plays a role in the zymosan-induced peritonitis and cardiovascular derangements in the rats.

Acute Disease↗

PubMed1996

Distribution of endothelin-1-receptor subtypes in rat portal vein.

Endothelin-1 (ET-1), a potent vasoactive peptide, was first isolated from cultured porcine endothelial cells. Subsequent studies revealed the existence of two additional related peptides, ET-2 and ET-3, and at least two distinct ET-receptor subtypes, ETA (selective for ET-1) and ETB (nonselective for ET isopeptides). These isopeptides and receptors are widely distributed in many tissues and are involved in numerous biological responses. The aim of this study was to identify the eventual distribution of the two distinct endothelin-receptor subtypes in isolated endothelium-denuded rat portal vein rings (PVRs) and strips (PVSs). BQ-123 (0.6, 1, and 6 microM) and PD-145065 (0.06, 0.1, 0.6, and 6 microM) were used to differentiate the subtypes because they are selective antagonists for ETA and nonselective antagonists for ETA-ETB receptors, respectively. To characterize the ET receptors further, sarafotoxin-S6c (a selective ETB-receptor agonist) and IRL-1038 (a selective ETB-receptor antagonist) were used. In PVRs, cumulative additions of ET-1 (0.1-100 nM) caused graded and slow contractions and potentiated spontaneous rhythmic contractions. The EC50 values and maximal response to 100 nM of ET-1 were 2.72 nM and 0.75 g, respectively (n = 7). PVSs showed ET-1 EC50 values very similar to those of PVRs, but Emax values to 100 nM of ET-1 were significantly lower (Emax = 0.33 g; n = 7). Moreover, ET-1 clearly increased the amplitude and frequency of spontaneous contractions in both types of specimens, although these were greater in the PVSs. Thirty-minute incubation with the selective ETA-receptor antagonist BQ-123 blunted ET-1-induced effects in PVS specimens but only weakly antagonized ET-1-induced contractions in PVRs. In contrast, the nonselective ETA-ETB-receptor antagonist PD-145065 significantly shifted the ET-1 concentration-response curve to the right in PVRs and partially inhibited ET-1 effects in PVSs. Moreover, sarafotoxin-S6c (0.1-100 nM) contracted PVRs and PVSs in a similar manner to ET-1; its effects were antagonized by IRL-1038 only at the PVR level. The differences observed in PVR and PVS specimens in response to agonists and antagonists of ET confirmed the great heterogeneity of endothelin-sarafotoxin receptors. In our experimental models, functionally ETB-like (or non-ETA) receptors seem mostly to mediate vasoconstriction.

Animals↗

PubMed1996

Beta-adrenoreceptor blocking heterocyclic oximes and ethers.

This paper reports synthesis and pharmacological properties of thienyl, pyrrol, indolyl and benzofuryl-O-(3-alkylamine-2-hydroxypropyl)oximes and some 3-(3-alkylamine-2-hydroxypropyl)alkyloxy indoles aiming to study the influence of five membered and condensed heterocyclic substituents on the beta-adrenoreceptor inhibiting potency. All heterocyclic derivatives synthesized (1-17) were less active than the reference propranolol on the rat heart, while showed a comparable potency on the guinea pig trachea, exhibiting a significant beta 2-selectivity. The low beta-blocking potency of the five membered derivatives seemed to confirm the negative influence of the polarization of the oximic carbon in the binding with non polar region of the beta-adrenoreceptor. Another important interaction could take place with the enzyme adenyl-cyclase which is responsible of the signal of transduction. It could be hypothesized that the heteroatom of the heterocyclic nucleus acted as an electron-donor group and engaged a coordinative bond with magnesium atom present on the adenylcyclase system, responsible of the agonist activity. The pharmacological in vivo experiments and the binding results were in accordance with the in vitro data.

Adrenergic beta-Antagonists↗

PubMed1995

Nitric oxide participates in the hypotensive effect induced by adenosine A2 subtype receptor stimulation.

In a previous study, we demonstrated that adenosine plays an important role in the central control of the cardiovascular system with involvement of adenosine A2 rather than A1 subtype receptors. In the present study, we investigated the putative relationship between nitric oxide (NO) and adenosine in the central and peripheral control of the cardiovascular system. Adult male normotensive anesthetized rats were treated with N6-cyclohexyladenosine (CHA), an A1-purinoceptor agonist, and 5'-N-cyclopropyl-carboxamidoadenosine (CPCA), an A2-purinoceptor agonist intracerebroventricularly (i.c.v. 3rd ventricle; 0.05-0.1-0.5 microgram/rat) and by intravenous injection (0.5-1-5 microgram kg-1 i.v.). CPCA and CHA induced a significant and dose-dependent decrease in arterial blood pressure (BP). CHA effects were less marked than CPA. Rats were pretreated with xanthine amine congener (XAC), and A1 adenosine antagonist, with 3,7-dimethyl-1-propargylxanthine (DMPX), an A2 adenosine antagonist (both administered at doses of 0.05 microgram/rat i.c.v. or 0.5 microgram kg-1 i.v.) and with N omega-nitro-L-arginine methyl ester, an NO synthase inhibitor, (L-NAME, 90 microgram/rat i.c.v. and 0.3 mg kg-1 i.v.). The intracerebroventricular and intravenous pretreatment with DMPX or L-NAME inhibited CPCA-induced hypotension; the effect of L-NAME was weaker than that of DMPX. The L-NAME inhibitory effect was reversed both in the central nervous system (CNS) and at the peripheral level by pretreatment with L-arginine (L-Arg; 90 mg kg-1 i.v.), a precursor of NO synthesis. Pretreatment with XAC, but not with L-NAME, reduced the hypotensive effect of CHA. Moreover, intracerebroventricular pretreatment with L-Arg (174 micrograms/rat) increased the hypotensive effect of CPCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1995

Endothelin-1 in rat periaqueductal gray area induces hypertension via glutamatergic receptors.

We investigated the possible relationship between endothelin-1 injection into the dorsolateral periaqueductal gray area and the glutamatergic system in the control of cardiovascular function. Endothelin-1 was injected into the dorsolateral periaqueductal gray area of freely moving rats at doses ranging from 0.1 to 10 pmol. Endothelin-1 increased arterial blood pressure (from 7.0 +/- 1.6 to 55.0 +/- 4.1 mm Hg, mean +/- SEM) in a dose-dependent manner and induced characteristic behavioral changes such as longitudinal rolling of the body (barrel-rolling). DL-2-Amino-5-phosphonovaleric acid and (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[D-alpha] cyclohepten-5,10-imine hydrogen maleate, both selective N-methyl-D-aspartate excitatory amino acid receptor antagonists, but not 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, significantly decreased endothelin-1-induced cardiovascular and behavioral changes (P < .01). Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, also prevented these effects. We propose that the glutamatergic system may exert, via N-methyl-D-aspartate receptors, a significant influence on endothelin-1-induced cardiovascular and behavioral effects after its injection into the periaqueductal area.

Animals↗

PubMed1994

Vasomotor reactivity and catecholamine, arginine vasopressin plasma levels during ageing and development in rats.

Vascular reactivity, heart rate responses to vasoconstrictor and/or vasodilatator agents and catecholamine and arginine vasopressin turnover were studied in normotensive Wistar Kyoto (WKY), spontaneously hypertensive (SHR), normolipemic Brown Norway (BN) and spontaneously hyperlipemic Yoshida (YOS) anaesthetized rats at 2, 6 and 18 months of age. In this study, we investigated whether ageing and development could affect cardiovascular reactivity to vasoactive substances and catecholamine and arginine vasopressin turnover. No significant changes in the pressor responses to noradrenaline and to carotid sinus baroreceptor stimulation were observed nor were there significant alterations in reflex tachycardia and bradycardia. Arginine vasopressin plasma levels also did not change with ageing and development. On the other hand, the hypotensive responses to isoprenaline decreased in old rats, acetylcholine relaxation effect increased with ageing and development in some rat strains (BN and YOS) and catecholamine plasma levels increased with ageing and development. Our results indicate that during ageing and development, vascular responsiveness to vasoconstrictor and/or vasodilatator agents, as well as amine turnover, may increase, decrease or not change at all depending on the neurotransmission system studied, and on the experimental model and/or animal tested.

Acetylcholine↗

PubMed1994

Effects of the polyamine spermidine on NMDA-induced arterial hypertension in freely moving rats.

We investigated the effect of the polyamine spermidine (SPD) (0.01-1 microgram/rat) on hypertension induced by N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) microinjected into the latero-caudal periaqueductal gray (PAG) area of freely moving rats. Pretreatment with a low dose of SPD (0.01 microgram/rat) significantly increased NMDA-induced hypertension. On the contrary, higher doses of SPD (0.1 and 1 microgram/rat) significantly decreased NMDA-induced cardiovascular changes. SPD alone did not modify arterial blood pressure. Arcaine (1 microgram/rat), a putative antagonist at the polyamine recognition site on NMDA receptors, when microinjected into the PAG area, prevented the negative but not the positive modulatory effects of SPD on the NMDA-induced cardiovascular changes. Pretreatment with SPD did not affect cardiovascular effects induced by quisqualic acid (QUIS), a non-NMDA receptor agonist. These data, in agreement with the in vitro results, suggest that at the level of the PAG area, the polyamines also show multiple actions at NMDA receptors in vivo.

Animals↗

PubMed1994

Relation between L-arginine-nitric oxide pathway and endothelin-1 effects in periaqueductal gray area of rats.

Injection of N omega-nitro-L-arginine methyl ester (L-NAME), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) synthase, in dorsolateral periaqueductal gray (PAG) area of freely moving rats at doses from 0.1 to 1 mumol per rat, dose-dependently increased arterial blood pressure (BP). Endothelin-1 (ET-1) injected in the same area at doses from 0.1 to 1 pmol per rat also induced pressor effects. Administration of L-NAME (1 mumol per rat) in the PAG area 10 min before ET-1 significantly (p < 0.01) potentiated ET-1-induced hypertension. Pretreatment with L-arginine (1 mumol per rat), precursor of NO, significantly (p < 0.01) decreased L-NAME-induced potentiation of ET-1 pressor effects. L-Arginine also prevented the ET-induced increase in arterial BP and reversed L-NAME-induced hypertensive effect. Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, reduced either ET-1 or L-NAME pressor effects. Our data suggest the presence of NO synthase in the PAG area, considered an important cerebral area in coordinating physiologic responses such as cardiovascular and respiratory adjustment. Moreover, our results suggest that even at the PAG area level, functional antagonism exists between NO and ET-1, possibly contributing, through sympathetic outflow, to central regulation of arterial BP.

Animals↗

PubMed1994

Cardiotoxicity of doxorubicin: effects of drugs inhibiting the release of vasoactive substances.

The therapeutic usefulness of doxorubicin, an antineoplastic drug, is limited by its cardiotoxicity whose mechanism is as yet unknown. Several hypotheses have been postulated including also the release of vasoactive substances, so the aim of the present investigations was to study the relationship between the release of vasoactive substances and the development of doxorubicin-induced cardiotoxicity. The effects of the following drugs on doxorubicin-induced (cumulative dose of 20 mg/kg intraperitoneally) cardiotoxicity in rats have been evaluated: verapamil (1 and 10 mg/kg orally), that inhibits the slow channel influx of calcium and catecholamine release, acetylsalicylic acid (50 and 100 mg/kg orally), that inhibits the prostaglandin biosynthesis and release, and cromolyn sodium (cromolyn; 1 and 10 mg/kg orally), that inhibits the secretion of histamine. Our results showed that verapamil reduced and delayed doxorubicin-induced mortality, and limited doxorubicin-induced body weight decrease and ECG changes. Acetylsalicylic acid and cromolyn did not protect against doxorubicin-induced cardiotoxicity. These findings suggest that the release of vasoactive substances does not play a prevalent role in the development of doxorubicin-induced cardiotoxicity. The protective effect of verapamil is probably due to the inhibition of doxorubicin-induced intracellular calcium overload.

Animals↗

PubMed1994

3,5-Diphenyl-1H-pyrazole derivatives. XII. N-substituted 4-amino-1-(2-hydroxy- or 2-alkylaminoethyl)-3,5-diphenyl-1H-pyrazoles with local anesthetic, analgesic and platelet antiaggregating activities.

The synthesis of 4-amino-3,5-diphenyl-1H-pyrazole-1-ethanol, as well as of their N-methyl, N-ethyl and N,N-dimethyl derivatives is described. A series of 1-(2-alkylaminoethyl)-3,5-diphenyl-1H-pyrazole-4-amines and of N-substituted 4-dimethylamino-3,5-diphenyl-1H-pyrazole-1-ethanamines were also prepared. Some of the above compounds showed remarkable local anesthetic, analgesic and in vitro platelet antiaggregating activities, as well as moderate antiinflammatory and antipyretic activities in rats and mice.

Analgesics↗