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At least 19 recordsLinked to original sources

PubMed1996

Effects of single oral doses of lysine clonixinate and acetylsalicylic acid on platelet functions in man.

Lysine clonixinate is an analgesic drug with a so far unknown mechanism of action. We have determined its effect on platelet cyclooxygenase in man. Biosynthesis of thromboxane (TX)B2 and prostaglandin (PG)F2 alpha in clotting whole blood ex vivo as well as collagen-induced platelet aggregation measured before and at various time points after oral administration of 125 mg lysine clonixinate were compared to results obtained with 500 mg acetylsalicylic acid (ASA). While biosynthesis of both TXB2 and PGF2 alpha measured radioimmunologically was inhibited significantly 2.5 h, but not 6 h, after administration of lysine clonixinate, inhibition by ASA was much greater and still highly significant after 48 h. Similarly, collagen-induced aggregation of platelet-rich plasma was inhibited for a longer period and to a greater extent after administration of ASA than after lysine clonixinate. Our results indicate that lysine clonixinate is a cyclooxygenase inhibitor of moderate potency. It remains to be investigated whether mechanisms other than inhibition of cyclooxygenase contribute to the analgesic activity of lysine clonixinate.

Administration, Oral↗

PubMed2005

Interaction of clonixin with EPC liposomes used as membrane models.

In this work, an overall analysis of clonixin interaction with liposomes was achieved using different techniques, which allowed the evaluation of the change in different membrane's characteristics as well as the possible location of the drug in the membrane. Clonixin acidity constants were obtained and the values are 5.5 +/- 0.08 and 2.2 +/- 0.04. Clonixin partition coefficient (K(p)) between liposomes and water was also determined using derivative spectrophotometry, fluorescence quenching, and zeta-potential (zeta-potential). These three techniques yielded similar results. zeta-potential measurements were performed and an increase of the membrane negative charge with an increase of drug concentration was observed. Drug location within the bilayer was performed by fluorescence quenching using a set of n-(9-anthroyloxy) fatty acid probes (n = 2, 6, 9, and 12). The fluorescence intensity of all probes was quenched by the drug. This effect is more noticeable for the outer located probe, indicating that the drug is positioning in the external part of the membrane. These same probes were used for steady-state anisotropy measurements to determine the perturbation in membrane structure induced by clonixin. Clonixin increased membrane fluidity in a concentration dependent manner, with the highest perturbation occurring nearby the 2-AS probe, closely located to the bilayer surface.

Clonixin↗

PubMed1995

Effects of lysine clonixinate and ketorolac tromethamine on prostanoid release from various rat organs incubated ex vivo.

The release of prostanoids from rat brain, gastric mucosa, lungs and kidneys incubated ex vivo has been investigated for up to 5 h after oral administration of 10 mg/kg lysine clonixinate or 1 mg/kg ketorolac tromethamine. Additionally, 60 min after drug administration, a time point of near-maximal inhibition of prostanoid release, the effects of 2.5, 10 and 30 mg/kg lysine clonixinate and of 0.0225, 0.15 and 1 mg/kg ketorolac tromethamine were compared. In all organs investigated both drugs inhibited fatty acid cyclooxygenase (COX) in a dose-dependent manner, but ketorolac tromethamine was more potent and had a longer-lasting effect than lysine clonixinate. While the ID50 values for lysine clonixinate were in the same order of magnitude for all 4 organs investigated, ketorolac tromethamine exhibited some organ selectivity with a particularly high activity in the kidneys. This effect might be related to the renal toxicity of ketorolac tromethamine. On the other hand, the difference in potency was smallest in brain suggesting that inhibition of central prostanoid biosynthesis could contribute to the rapid and effective inhibition of pain by both drugs. IC50 values for inhibition of purified COX-1 and COX-2 in vitro were slightly lower for lysine clonixinate (2.4 and 24.6 micrograms/ml, respectively) than for ketorolac tromethamine (3.7 and 25.6 micrograms/ml, respectively).

6-Ketoprostaglandin F1 alpha↗

PubMed2001

Effect of lysine clonixinate on the pharmacokinetics and anticoagulant activity of phenprocoumon.

The effect of the non-steroidal anti-inflammatory drug lysine clonixinate ([2-(3-chloro-o-toluidino)nicotinic acid]-L-lysinate, CAS 55837-30-4) on the pharmacokinetics and anticoagulant activity of phenprocoumon (4-hydroxy-3-(1-phenylpropyl)-coumarin, CAS 435-97-2) was investigated in an open, randomised, two-fold, cross-over study in 12 healthy male volunteers. These subjects received a single dose of 18 mg phenprocoumon without or with concomitant treatment with lysine clonixinate (125 mg five times a day for 3 days before and 13 days after ingestion of a single dose of phenprocoumon). Pharmacokinetic parameters of phenprocoumon following oral administration were: CL/f: 0.779 +/- 0.157 ml/min, half-life of elimination: 147.2 +/- 19.9 h; free fraction in serum: 0.51 +/- 0.20%. These parameters were not significantly altered by concomitant treatment with lysine clonixinate. Prothrombin time increased from 13.3 +/- 1.3 s (at time 0) to 17.7 +/- 2.7 s following phenprocoumon and from 13.3 +/- 1.2 s to 18.0 +/- 2.2 s following combined administration. Prothrombin time returned to the pretreatment values 240 h after administration of phenprocoumon. The integrated effect (AUEC0-288 h) was identical following both treatments (4.303 +/- 461 and 4.303 +/- 312 s x h for phenprocoumon alone and phenprocoumon with lysine clonixinate, respectively). Thus, lysine clonixinate administered in therapeutic doses does not affect the pharmacokinetics and anticoagulant activity of phenproxoumon.

Adult↗

PubMed1998

Efficacy and tolerance of lysine clonixinate versus paracetamol/codeine following inguinal hernioplasty.

In this study lysine clonixinate, a nonsteroidal antiinflammatory agent with selective inhibition of cyclooxygenase-2 and 5-lipooxygenase in in vitro and in vivo pharmacodynamic studies, was evaluated in a prospective, randomized, double-blind, double-dummy clinical study versus paracetamol/codeine, in 151 patients with pain following inguinal hernioplasty. Patients were treated with one 125 mg tablet of lysine clonixinate or paracetamol/codeine (500 mg + 30 mg) administered at fixed doses every 4 h during 2 days. Controls were carried out 1, 2 and 4 h after the first intake of day 1 and day 2. Each control included assessment of pain at rest, when coughing, sitting and upon moderate pressure. Both treatment groups (lysine clonixinate, 77 patients and paracetamol/codeine, 74 patients) were comparable in terms of demographic and baseline pain intensities. Spontaneous pain was reduced significantly in both treatment groups from the 1st-h control. The following values were recorded in the lysine clonixinate group during day 1: baseline: 6.86 +/- 1.24; 1st h: 4.49 +/- 1.77; 2nd h: 2.96 +/- 1.74; 4th h: 2.23 +/- 1.51. The following values for the same group during day 2 were: predose: 1.70 +/- 1.64; 1st h: 1.16 +/- 1.17; 2nd h: 0.78 +/- 1.06; 4th h: 0.63 +/- 1.05. The paracetamol/codeine group revealed the following values: day 1: baseline: 6.72 +/- 1.22; 1st h: 4.57 +/- 1.72; 2nd h: 2.97 +/- 1.68; 4th h: 2.47 +/- 1.68 and day 2: predose: 2.02 +/- 1.57; 1st h: 1.32 +/- 1.23; 2nd h: 0.82 +/- 0.99; 4th h: 0.66 +/- 0.89. Reduction of pain induced by coughing, sitting and pressure showed similar behavior patterns. No significant differences between both treatment groups were encountered in terms of analgesic efficacy. Incidence of adverse effects was significantly higher in the paracetamol/codeine group (X2: p < 0.05): 11 out of 74 patients; three patients had to discontinue treatment. In the lysine clonixinate group four out of 77 patients showed side effects but these did not require treatment discontinuation.

Acetaminophen↗

PubMed1975

Lack of effect of rheumatoid arthritis on clonixin metabolism.

The effect of rheumatoid arthritis on the metabolism of the analgesic, 2-(3-chloro-o-toluidino) nicotinic acid (clonixin), was evaluated in 12 patients with rheumatoid arthritis and in 12 matched healthy control subjects. Males, age-matched by decades, had no renal, gastrointestinal, or hepatic disease, and took no drugs during the study. Lower (p less than 0.02) serum albumins and higher globulins in the patients (albumin: 3.87 plus or minus 0.18; globulin: 3.14 plus or minus 0.28 gm/100 ml) than in the control subjects (albumin: 4.42 plus or minus 0.10; globulin: 2.36 plus or minus 0.08 gm/100 ml) were considered to be manifestations of rheumatoid arthritis. Fasting subjects were given single oral doses of 750 mg of clonixin. A spectrophotometric method was used to determine drug blood levels. Serum half-life was 1.45 plus or minus 0.12 hr in patients and 1.50 plus or minus 0.13 hr in control subjects (p greater than 0.5). Mean peak concentration developed at 1.7 hr and was 40.0 plus or minus 2.6 mug/ml for patients and 46.1 plus or minus 3.1 mug/ml for control subjects. Thus a single oral dose of clonixin results in comparable blood levels in male patients suffering from rheumatoid arthritis and in healthy control subjects.

Adult↗

PubMed1976

Effect of clonixin and aspirin on platelet aggregation in human volunteers.

The effect of clonixin and aspirin on platelet function was assessed in healthy volunteers. Both drugs inhibited secondary platelet aggregation and prolonged bleeding time, but the effect of clonixin was significantly less than that of aspirin. Hemorrhagic complications are less likely after clonixin than after aspirin.

Adenosine Diphosphate↗

PubMed2000

Determination of clonixin in plasma and urine by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method that enables the determination of clonixin in human plasma and urine samples is described. Recovery of the drug was over 87.6 and 80.7% for plasma and urine, respectively. The limit of quantitation of the method was established as 10 ng/ml in plasma and 20 ng/ml in urine samples, with RSDs of less than 11.1%. The applicability of the method was further assessed by determining the plasma concentrations time course of clonixin in six healthy volunteers after single oral dose administration of 150 and 300 mg of clonixin and Clonix.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Extraction and LC determination of lysine clonixinate salt in water/oil microemulsions.

A new reversed-phase high performance liquid chromatography method has been developed and validated for the quantitative determination of lysine clonixinate salt in water/oil microemulsions. The mobile phase was acetonitrile-buffer phosphate pH 3.3. Detection was UV absorbance at 252 nm. The precision and accurately of the method were excellent. The established linearity range was 5-60 microg ml(-1) (r(2)=0.999). Microemulsions samples were dispersed with chloroform and extracted lysine clonixinate salt with water. This easy method employing chloroformic extraction has been done three times. The recovery of lysine clonixinate salt from spiked placebo and microemulsion were >90% over the linear range.

Analgesics↗

PubMed1996

Pharmacokinetics of lysine clonixinate in children in postoperative care.

The pharmacokinetics of 2 doses of intravenous lysine clonixinate (4 and 6 mg x kg-1) were studied in 10 children (age 4-10 years) under postoperative care. A single dose of the drug was injected in a forearm vein. Blood samples were collected at regular intervals for 3 hours. Serum clonixin concentrations (expressed as clonixin) were analyzed using a high pressure liquid chromatography method. Pharmacokinetic values were estimated by a nonlinear computer program. The distribution volume was similar in both groups of children (1.288 +/- 0.829 1 and 1. 139 +/- 0.667 1, respectively). There were no differences between the values of total plasma clearance and the administered doses (0.026 +/- 0.017 ml x min-1 and 0.017 +/- 0.008 ml x min-1, t = 1.07, p = 0.76). The elimination half-life was longer in children who received 6 mg x kg-1 (44.26 +/- 6.34 min vs 38.63 +/- 10.93 min) but this difference was not statistically significant (t = 0.99, p < 0.34). The pharmacokinetic parameters calculated in these children were different from those found by other authors in adults and experimental animals.

Age Factors↗

PubMed1992

Effects of clonixin on the electrical activity of cardiac pacemaker cells.

1. The electrophysiological effects of clonixin, a non-steroidal analgesic, on cardiac pacemaker cells of spontaneously beating frog sinus venosus, were studied by intracellular recording of transmembrane potentials. 2. Results show that clonixin (Clx) between 1 x 10(-6) M and 3 x 10(-4) M, decreases the OS, APA, Vmax and frequency of primary and subsidiary cells, however pacemaker cells differ in their sensitivity to Clx. 3. At 2 x 10(-6) M, Clx completely blocked the spontaneous beating of primary cells. It is necessary to increase the Clx concentration about two orders of magnitude in order to attain a similar degree of blockade of subsidiary cells. 4. Previous or simultaneous superfusion with atropine does not modify Clx effects, thus a probable cholinergic mechanism of action for Clx is discarded. 5. When Clx concentrations were lower than 5 x 10(-4) M, their effects on both types of cells were partially reversed by a 100% increase of external calcium concentration. 6. BAY K-8644 which stimulates calcium influx through calcium L-type channels, reverted Clx effects on pacemaker cells. 7. It is suggested that Clx blocks calcium inward current which generates all or part of the upstroke of primary cells and subsidiary ones, respectively.

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

PubMed1999

Site-specific effects of the nonsteroidal anti-inflammatory drug lysine clonixinate on rat brain opioid receptors.

In addition to effects in the periphery through inhibition of prostaglandin synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) act in the central nervous system. The possibility that the central action of NSAIDs involves regulation of opioid receptors was investigated by quantitative autoradiography of mu, delta, and kappa sites in rat brain slices. Increased (p < 0.05) labeling of mu receptors was observed in thalamic nuclei, gyrus dentate, and layers of the parietal cortex of rats treated for 10 days with lysine clonixinate. Labeling of delta receptors was lower in the lateral septum, and kappa sites decreased in thalamic nuclei. These effects were not mediated through direct interaction with opioid-binding sites, since receptor-binding assays using rat brain membranes confirmed that clonixinate up to 1 x 10(-4) mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central effects of NSAIDs might, therefore, involve interaction with the opioid receptor system through indirect mechanisms.

Analgesics↗

PubMed2001

Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study.

Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, were studied prospectively. Patients received LC or placebo once the headache reached moderate or severe intensity for 6 consecutive attacks. With regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4 hours. The consumption of other rescue medications after 4 hours was significantly higher in the placebo group. With regard to the severe attacks, there was no difference between the active drug group and the placebo group concerning headache intensity and consumption of other rescue medications. We conclude that the NSAID lysine clonixinate is effective in treating moderately severe migraine attacks. It is not superior than placebo in treating severe migraine attacks.

Administration, Oral↗

PubMed2001

[Effects of lysine clonixinate on platelet function. Comparison with other non-steroidal anti-inflammatory agents].

One of the mechanisms of action of non steroid antiinflammatory drugs (NSAIDs) consists of inhibition of prostaglandin synthesis. This explains many of the pharmacological effects and adverse events observed in medical practice. Administration of NSAIDs to patients with hemostatic disorders or perioperative conditions entails the risk of bleeding due to inhibition of platelet function. This study deals with platelet changes induced by lysine clonixinate vs diclofenac, ibuprofen and aspirin in classical tests such as platelet count, platelet factor 3 (PF3) activity and platelet aggregation with various inductors and more recent procedures such as P-selectin measurement by flow cytometry. Unlike control drugs, lysine clonixinate did not induce changes in platelet count or function when administered to healthy volunteers at the commonly used therapeutic doses.

Adult↗

PubMed1993

Lysine clonixinate in minor dental surgery: double-blind randomized parallel study versus paracetamol.

Lysine clonixinate (LC), an effective and well tolerated non-morphinic analgesic whose mechanism of action is basically due to the inhibition of cyclo-oxygenase, was assessed with a double-blind randomized dummy design versus paracetamol (P) on 200 patients suffering from pain after minor dental surgery. Patients received according to their needs 1 or 2 tablets of 125 mg lysine clonixinate or 500 mg paracetamol every 8 h during 48 h or until pain relief. Both groups, each composed of 100 patients, were comparable in terms of demographic conditions (t test), initial symptoms (chi-square test), characteristics of the extracted dental pieces, surgical complications and wound treatment (chi-square test). Pain intensity scores and daily average intake of tablets (3.4/day) documented in the patients' diary revealed no statistically significant differences between the two treatments (chi-square test). It was found that spontaneous pain measured using a visual analogue scale (VAS) decreased significantly in both treatment groups at the 24-h control examination. The following values were observed in the LC group: baseline 4.38 +/- 1.7; 24-h * 1.20 +/- 1.4; 48-h * 0.36 +/- 1.2. In the P group the values were: baseline 4.28 +/- 1.6; 24-h * 1.11 +/- 1.4; 48-h * 0.30 +/- 0.7 (*p < 0.05). Other variables like facial swelling and night pain, evaluated on a score from 0 to 4 and symptom presence or absence respectively, showed a similar response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

PubMed1998

[Analgesic-antispasmodic effect and safety of lysine clonixinate and L-hyoscinbutylbromide in the treatment of dysmenorrhea].

The purpose of this longitudinal open but not comparative study was to confirm the safety and efficacy of Lysine clonixinate (125 mg) and hyoscinbutylbromide (10 mg) capsules, during a period of observation of there menstrual cycles on 30 women with uterine dysfunction due to primary or secondary dysmenorrhea. The time of evolution for primary dysmenorrhea was of 4.46 years, and for secondary was of 1.77 years. Some associated manifestations of dysmenorrhea were: nausea (92%), vomit (92%), general pain (82.1%), abdominal pain (85.7%) and headache (46.4%). Regarding to the menstrual pain intensity, at first was highly severe in 10.7% severe in 42.9%, and moderate in 46.4%. At the end of the study, only 1 of 28 patients showed menstrual pain of moderate intensity. Only three adverse effects of light intensity were found without needing treatment, related to the manifestations of gastralgia and sleepiness. The association of a spasmolytic analgesic (Lysine clonixinate and hyoscinbutylbromide bromide) on the treatment for primary or secondary dysmenorrhea, reduces and prevents the menstrual pain (colic) as well as the associated manifestations with few spasmolytic association is efficacy and safety.

Administration, Oral↗

PubMed2001

In vivo and in vitro effects of lysine clonixinate on nitric oxide synthase in LPS-treated and untreated rat lung preparations.

Recent studies have shown that some nonsteroidal antiinflammatory drugs (NSAIDS) inhibited the inducible NO synthase (iNOS) without direct effect on the catalytic activity of this enzyme. This study was conducted to investigate the in vitro and in vivo effects of lysine clonixinate (LC) and indomethacin (INDO) on NOS activity in rat lung preparation. LC is a drug with antiinflammatory, antipyretic, and analgesic action. In the in vitro experiments, rats were injected with saline or lipopolysaccharide (LPS) and killed 6 h after treatment. Lung preparations were incubated with LC at 2.3 x 10(-5) M or 3.8 x 10(-5) M. The minimum concentration did not modify NOS activity in control or LPS-treated rats but the maximum dose inhibited increased NO production induced by LPS. Furthermore, INDO at 10(-6) M had no effect on enzymatic activity in control or LPS-treated rats. In the in vivo experiments, 40 mg/kg of LC were injected ip. Such a dose did not affect basal production of NO. When LC and LPS were injected simultaneously 6 h before sacrifice, a significant decrease in LPS-induced NOS activity was observed. INDO 10 mg/kg injected in control animals had no effect on NOS activity and did not block LPS induced stimulation of NO production when injected simultaneously. Finally, when LC (40 mg/kg) was injected 3 h after LPS, the enzymatic activity remained unchanged. Expression of iNOS was detected by Western blotting in rats treated with LPS plus 4, 10, 20, and 40 mg/kg of LC. The lowest dose was the only one showing no effect on LPS-induced increase of iNOS. In short, LC is a NSAID with inhibitory action on the expression of LPS-induced NOS, effect that was not seen with INDO in our experimental conditions.

Animals↗

PubMed1993

Effects of flunixin and mefenamic acid on cardiac pacemaker cells. Structure-activity relationship and comparison with clonixin.

1. The electrophysiological effects of flunixin and mefenamic acid, non-steroidal analgesics, on frog cardiac pacemaker cells, were studied by intracellular action potential recording. 2. Results show that flunixin (Flx) between 2 x 10(-6) and 1 x 10(-4) M, exerts a frequency, OS, APA and Vmax concentration-dependent decrease, similar to the effects of clonixin (Clx) reported elsewhere (Morales et al., Gen. Pharmac. 23, 515-521, 1992). 3. At 2.5 x 10(-4) M, Flx induces a complete cessation of the electrical activity of subsidiary pacemaker cells. 4. Mefenamic acid (Mef), in spite of its structural similarity with Clx and Flx, induces no appreciable electrophysiological changes. 5. Flx effects were partially reversed by increasing external calcium concentration and fully antagonized by BAY K-8644, a calcium L-type channel agonist. 6. By comparing the structures of the three fenamates studied, it is suggested that the nitrogen of the heterocycle and the electron-donor capacity of the bencenic ring are essential features for the calcium-antagonist activity of Clx and Flx.

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