Antispasmodic action of propinox on the isolated human gallbladder: possible mechanism of action

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the galbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallblader and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03x10(-8) M>propinox 1.25x10(-7) M> verapamil 6.63x10(-6)M> (-) scopolamine-n-butyl1 bromide 5.4x10(-5) M. pD'2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antisplasmodic action of the drug involved binding to muscarinic receptors or calciumatagonist sites. The inhibition constant (Ki) of proponix for muscarinic receptors of guinea pig ileum smoth muscle, which contains a mixed M2-M3 receptor population, was 1.6x10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0x10(-4) M, for cardiac receptors (M1) was 1.0x10(-4)M, for receptors (M2) 1.2x10(-6)M and from salivary gland receptors (M3) 1.5x10(-6)M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9x10(-5)M for propinox and 2.2x10(-7)M for verapamil. For the phenylakylamine binding sites Ki were: 5.0x10(-6)M for propinox and 3.5x10(-8)M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2x10(-6)M. The following may be concluded: 1- The antispasmodic activity of propinox in isolated human galbladder was was comparatively less potent than of atropine and more potent than those verapamil and (-) scopolamine-n-butyl bromide. 2- Propinox showed binding to muscarinic and calcium receptors that can be related to its antisplasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.- The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.

Lysine clonixinate vs. paracetamol / codeine in postepisiotomy pain

This study conducted to compare the analgesic action of Lysine Clonixinate (LC) vs Paracetamol/Codeine association (PC) in the treatment of postepisiotomy pain in primiparae women: 131 primiparous patients with moderate-to-severe postepisiotomy pain were enrolled in a double blind dummy design study and randomly allocated to either treatment with fixed doses of LC 125 mg or Paracetamol 500 mg+Codeine 30 mg 6 qh during 24 hours. Intensity of spontaneous pain and pain on walking was assessed according to a visual analog scale (VAS) and patientÝs assessment before receiving treatment and after 1, 2, 6 and 24 hours. Intensity of spontaneous pain was reduced in 24 hours from 4.28+2.11 to 1.73+1.46 (P<0.0001) in the LC group and from 4.78+2.08 to 1.90+1.72 in the PC- treated group (p<0.0001); with no significant differences between treatments. 54 percent of the patients treated with LC and 55 percent of those receiving PC showed onset of analgesic action 30 minutes following dose administration. PatientÝs final global assessment revealed that 95 percent of LC-treated patients and 96 percent of the PC group showed total or partial pain relief during the first treatment day. No sleep disturbances were seen during the night in 75 percent of patients. Only one patient reveiving LC showed nausea not requiring treatment discontinuation. It is concluded that both treatments are equally effective to relieve moderate-to-severe postepisiotomy pain.

Lysine clonixinate in the treatment of primary dysmenorrhea

The efficacy tolerance of Lysine Clonixinate (LC), a NSAID with prostaglandin synthesis inhibiting mechanism was studied in 24 patients with primary dysmenorrhea according to a double-blind randomized crossover Placebo (P) controlled design with patients serving as their own controls. Treatment consisted in administering 1 tablet of LC or P q6h as from onset of menstrual pain during 5 days and 6 menstrual cycles. Patients were controlled monthly as from the 5th day of the cycle rating changes in pain intensity according to a 4-point scale, presence of pain during pre-, post-and menstrual periods: possible intracycle changes, amount of bleeding, tolerance and related total and general signs and symptons. Intensity of baseline menstrual pain amounted to 2.9. Menstrual, intramenstrual and postmenstrual pains were observed in 19 out of 24,24/24 and only 2 out of the patients, respectively. Concomitant symptons consisted in headache (12), mastalgia (14) and disconfort (12). Results were obtained by averaging the data from the 3 tratment periods with each drug. Menstrual pain was reduced from 2.9 + 0.7 to 1.9 + 0.7 with P administration and to 0.66 + 0.4 with the administration of LC, a highly significant difference between tratments (p<0.0001). Premenstrual pain was reduced nonsignificantly from 0.79 per cent to 0.58 per cent with P administration and significantly to 0.29 per cent with administration of LC (p<0.001). Intramenstrual pain affection all patients at baseline was reduced significantly by 8 per cent with P and also significantly by 50 per cent with LC p<0.001). No differences were encontered in encomitant symptoms during P treatment periods while the incidence was significantly reduced with LC (p<0.0001). No changes in cycle duration or amount of bleeding were observed between treatments. No adverse events were reported.

Clonixinato de lisina en gonartrosis / Effects of lysine clonixinate in gonartrosis

Se estudiaron en cinco centros 199 pacientes (CL 101,198)de ambos sexos entre 22 y 80 años con gonartrosis uni o bilateral dolorosa, con previo consentimiento escrito para participar. El tratamiento consistió en una semana de placebo y cuatro semanas de activo con CL 125 mg ó 1400 mg, 1 ó 2 comprimidos juntos cada 8 horas según necesidad. La respuesta terapéutica se estimó escalas visuales análogas y consumo de comprimidos registrados por los pacientes en un diario y en cuatro exámenes en consultorio. El grupo (CL) comprendió 29 varones y 72 mujeres con edad 61,44 ñ años, éso 74,84 ñ 11 Kg y talla 164 ñ 7,29 cm; el grupo (l) 21 varones y 77 mujeres con edad 62,41 ñ 7,39 años, peso 74,8 ñ Kg y talla 163 ñ 7 cm (Ji cuadrado y test NS). Los registros de escala visual análoga basales fueron semejantes; a partir del 2do. día se obsevaron diferencias de alta significancia entre los datos de cada día y los basales dentro de cada tratamiento pero sin diferencias entre tratamientos. Igual comportamiento se constató en los signos y síntomas explorados por los ensayistas en cada una de las 5 consultas de control. Los efectos adversos más frecuentemente se manifestaron en la esfera digestiva y neurológica, sin diferencias entre tratamientos. Clonixinato de lisina es un fármaco eficaz y de muy buena tolerancia, semejante al Ibuprofeno, útil para el control del dolor de la gonartrosis

Clonixinato de lisina en esguince de tobillo / Lisina clonixinate in sprain of ankle

Se estudiaron en 8 centros 195 pacientes (CL:97,1:98) de ambos sexos, entre 18 y 50 años con esguinces agudo de tobillo. El tratamiento duró 7 días durante los que se administraron CL 125 mg ó 1400 mg 1 ó 2 comprimidos juntos cada 8 horas según necesidad. La respuesta terapéutica se evaluó mediante escala visual análoga (EVA) completada por los pacientes, recuento de comprimidos no utilizados y 3 exámenes objetivos en consultorio en los que se consideró el dolor espontáneo y al movimiento, la tumefacción articular, el hematoma, el dolor a la palpación y la limitación de la movilad activa. Los signos y los síntomas pretratamiento fueron de valores semejantes en ambos grupos para todas las variables consideradas, lo que corrobora la correcta asignación al azar. A lo largo de la experiencia tanto en los autocontroles diarios como en la evaluación objetiva del 3er. y 8vo. día se observan mejorías significativas dentro de cada tratamiento con respecto a los valores basales, pero ausencia de diferencias entre tratamientos. La latencia de acción analgésica fue de 15 a 30 minutos en la mayoría de los pacientes de ambos grupos, con un intervalo menor para CL que para I. No hubo interrupción de tratamiento por intolerancia; los efectos adversos menores más frecuentes fueron de la esfera digestiva y neurológica. El consumo de comprimidos en dosis simple o doble no difirió entre grupos. Clonixinato de lisina 125 mg es un analgésico útil en el control de dolor del eguince de tobillo, con una eficacia y tolerancia semejantes a la del Ibuprofeno 400 mg