Synergistic interaction between diclofenac and pyrilamine on nociception, inflammation, and gastric damage in rats.

Experiments using nonsteroidal anti-inflammatory drugs (NSAIDs) alone have produced limited antinociceptive effects in animal models. For this reason, the number of studies involving the administration of NSAIDs along with an adjuvant drug harboring different mechanisms of action has increased enormously. Here, combinations of diclofenac and pyrilamine were used to determine their influence on nociception (formalin test), inflammation (paw inflammation produced by carrageenan), and gastric damage in rodents. Diclofenac, pyrilamine, or combinations of diclofenac and pyrilamine produced antinociceptive and anti-inflammatory effects in the rat. The systemic administration of diclofenac alone and in combination with pyrilamine produced significant gastric damage. Effective dose (ED) values were determined for each individual drug, and isobolograms were prepared. The theoretical ED values for the antinociceptive (systemic, 35.4 mg/kg; local, 343.4 µg/paw) and the anti-inflammatory (37.9 mg/kg) effects differed significantly from the experimental ED values (systemic antinociception, 18.1 mg/kg; local antinociception, 183.3 µg/paw; anti-inflammation, 10.6 mg/kg). Therefore, it was concluded that the interactions between diclofenac and pyrilamine are synergistic. The data suggest that the diclofenac-pyrilamine combinations can interact at the systemic and local peripheral levels, thereby offering a therapeutic alternative for the clinical management of inflammatory pain.

Naproxen, paracetamol and pamabrom versus paracetamol, pyrilamine and pamabrom in primary dysmenorrhea: a randomized, double-blind clinical trial. / Naproxeno, paracetamol y pamabrom versus paracetamol, pirilamina y pamabrom en dismenorrea primaria: estudio aleatorizado, doble ciego.

INTRODUCTION: Dysmenorrhea is caused by the discharge of prostaglandins into the uterine tissue; therefore, non-steroidal anti-inflammatory drugs (NSAIDs) are the established initial therapy for dysmenorrhea. Dysmenorrhea therapy may include the administration of drug monotherapy or combination therapy. However, clinical scientific evidence on the efficacy of medications with two or three drugs combined is scarce or nonexistent. OBJECTIVE: To evaluate and compare the efficacy and safety of two oral fixed-dose combinations for the relief of the symptoms of primary dysmenorrhea among Mexican women. One of the combinations is widely used in Mexico (paracetamol, pyrilamine and pamabrom) and the selected comparison was a medication with naproxen sodium, paracetamol and pamabrom based on the pathophysiology of primary dysmenorrhea. METHODS: This was a single-centre, double blind, experimental, parallel group, randomized trial. Female patients with primary dysmenorrhea, older than 17 years and with pain intensity greater than 45 mm on a visual analogue scale, were included. The patients were then randomized to receive tablets with naproxen sodium, paracetamol and pamabrom or tablets with paracetamol, pyrilamine and pamabrom for one menstrual cycle. Patient evaluations of symptomatology and pain intensity were recorded throughout one menstrual period. Descriptive and inferential statistical analyses were utilized. RESULTS: An intention-to-treat population of 91 women, with a mean age of 21.3 ± 3.2 years, received paracetamol, pyrilamine and pamabrom tablets, and 98 participants, with a mean age of 21.0 ± 3.2 years, received naproxen sodium, paracetamol and pamabrom tablets. The participants’ assessments of pain on the Visual Analogue Scale during the menstrual cycle demonstrated a significant reduction in both treatment groups (p<0.05). There is no significant difference in efficacy between both groups (p>0.05). CONCLUSIONS: The results showed that both drug combinations were not different in reducing dysmenorrheic pain. Likewise, both treatments were well tolerated. Therefore, both treatments may be used for the treatment of primary dysmenorrhea.

INTRODUCCIÓN: La dismenorrea primaria es causada por la descarga de las prostaglandinas en el tejido uterino. Por lo tanto, los fármacos antiinflamatorios no esteroideos son la terapia inicial para la dismenorrea. El tratamiento para la dismenorrea puede incluir la administración de monoterapia o la combinación de fármacos. Sin embargo, la evidencia clínica científica sobre la eficacia de los medicamentos con dos o tres fármacos combinados es escasa o ausente. OBJETIVO: Evaluar y comparar la eficacia y seguridad de dos combinaciones, en dosis fija y oral para el alivio de los síntomas de la dismenorrea primaria en mujeres mexicanas. Basados en la fisiopatología de la dismenorrea primaria, se utilizó una combinación comercializada en México de paracetamol, pirilamina y pamabrom. El comparador seleccionado fue un medicamento que contiene naproxeno sódico, paracetamol y pamabrom. MÉTODOS: Se realizó un estudio en un solo centro, a doble ciego, experimental, paralelo y aleatorizado. Las pacientes con dismenorrea primaria que se incluyeron fueron mayores de 17 años de edad y con una intensidad del dolor mayor a 45 milímetros en una escala visual analógica. Las pacientes fueron aleatorizadas para recibir tabletas con naproxeno sódico, paracetamol y pamabrom o tabletas con paracetamol, pirilamina y pamabrom para un ciclo menstrual. Se evaluó la intensidad de la sintomatología y el dolor de las pacientes a lo largo de un período menstrual. Se utilizó análisis estadístico descriptivo e inferencial. RESULTADOS: Se incluyó una población con intención de tratar de 91 mujeres, con una edad media de 21,3 ± 3,2 años la cual recibió tabletas de paracetamol, pirilamina y pamabrom. Otras 98 participantes, con una edad media de 21,0 ± 3,2 años, recibieron tabletas de naproxeno sódico, paracetamol y pamabrom. Las evaluaciones de dolor de las participantes con la escala visual analógica durante el ciclo menstrual demostraron una reducción significativa en ambos grupos de tratamiento (p<0,05). No hubo diferencia significativa en la eficacia entre los dos grupos (p>0,05). CONCLUSIONES: Los resultados mostraron que ambas combinaciones de fármacos no fueron diferentes en reducir el dolor dismenorreico. Del mismo modo, ambos tratamientos fueron bien tolerados. Por lo tanto, ambos tratamientos se pueden utilizar para el tratamiento de la dismenorrea primaria.

Ginkgo biloba extract improves spatial memory in rats mainly but not exclusively via a histaminergic mechanism.

In order to clarify the mechanism of Ginkgo biloba extract (GBE) on learning and memory, we studied the effect of GBE on spatial memory deficits induced by diphenhydramine, pyrilamine and scopolamine using the eight-arm radial maze performance of rats, in comparison with donepezil. Total error (TE), reference memory error (RME) and working memory error (WME) were used as indices of spatial memory deficits. Both GBE and donepezil caused a potent antagonistic effect on the increase in TE, RME and WME induced by diphenhydramine. GBE and donepezil also antagonized scopolamine-induced spatial memory deficits. Although the antagonistic effect of GBE on pyrilamine-induced spatial memory deficits was weak, a significant difference was observed with TE and WME. However, donepezil caused no antagonistic effect on pyrilamine-induced memory deficits. From these findings, we concluded that the effects of GBE are mainly contributable to cholinergic activity and perhaps partly due to a histaminergic mechanism.

Acute paw oedema induced by local injection of adenosine A(1), A(2) and A(3) receptor agonists.

The present study used plethysmometry to examine oedema following local injection of selective adenosine A(1), A(2) and A(3) receptor agonists and inhibitors of adenosine metabolism into the hindpaw of the rat. N(6)-Cyclopentyladenosine and L-N(6)-phenylisopropyladenosine (A(1)), 2-[p(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS21680) (A(2A)) and N(6)-benzyl-5'-N-ethylcarboxamido adenosine (N(6)-B-NECA) (A(3)) all produced an increase in paw volume (N(6)N(6)-cyclopentyladenosine, L-N(6)CGS21680). At the highest dose, each agent also produced a systemically mediated suppression of oedema. Oedema by N(6)-cyclopentyladenosine was blocked by caffeine, 8-cyclopentyl-1,3-dimethylxanthine and enprofylline. Oedema by CGS21680 was blocked by caffeine and 8-cyclopentyl-1, 3-dimethylxanthine. Oedema by N(6)-B-NECA was blocked by enprofylline, but not by caffeine or 8-cyclopentyl-1, 3-dimethylxanthine, or by systemic administration of MRS 1191. Oedema by both N(6)-cyclopentyladenosine and N(6)-B-NECA was blocked by mepyramine, ketanserin and phentolamine, but that by CGS21680 was not. The adenosine kinase inhibitor 5'-amino-5'-deoxyadenosine and the adenosine deaminase inhibitor 2'-deoxycoformycin produced only a limited increase in paw volume, and this was blocked by caffeine. This study demonstrates an acute paw oedema response following local administration of adenosine A(1), A(2) and A(3) receptor agonists, which likely results from different mechanisms of action in each case.

Efficacy and safety of mepyramine-theophylline-acetate in the treatment of asthmatic crisis in children.

Mepyramine-theophylline-acetate (MTA), a theophylline derivative combined with an antihistamine, is used to treat patients with asthma. A double-blind, randomized, prospective, parallel-group study was conducted to evaluate the efficacy and safety of MTA in the treatment of asthmatic crisis in children 2 to 6 years of age. Forty patients with mild-to-moderate asthma were admitted to the study. The MTA group received 8 mg/kg per day of MTA by mouth in three divided doses for 7 days. The other group received 50 microL/kg per day of placebo in three divided doses for 7 days. Salbutamol (albuterol) syrup was used as the rescue drug if manifestations of asthma persisted. Both the MTA group and the placebo group had similar demographic characteristics at baseline. Both groups showed improvement of the asthma symptoms (cough, dyspnea, hypoventilation, and wheezing), as evaluated by the investigators at days 3 and 7. Patient diary scores showed earlier improvements in the MTA group than in the placebo group. Both groups showed improvement in peak flow at days 3 and 7 (P = 0.005). The control group used more doses of salbutamol than the MTA group on days 2 through 6 and globally (mean +/- SD, 6.79 +/- 9.11 doses vs 1.29 +/- 2.23 doses). The improvements in the placebo group were thought to be due to salbutamol. Three MTA patients dropped out of the trial, one because the parents felt that the treatment was not effective and two because of gastrointestinal manifestations (epigastric discomfort and vomiting). In the placebo group, two patients dropped out. One patient had epigastric discomfort and the other had to be treated in the emergency department for an exacerbation of the asthma. We conclude that MTA may be a good therapeutic option for the treatment of asthmatic crisis in children 2 to 6 years of age.

[Evaluation of the efficacy and safety of mepifylline in oral solution in children with mild and moderate asthmatic crises]. / Valoración de la eficacia y seguridad de la mepifilina en solución oral en niños con crisis de asma leve a moderada.

Efficacy and safety of mepiphylline, a derivative of theophylline, was evaluated in a group of children, aged 6 to 10 years, with mild or moderate acute asthma. A parallel, randomized, double-blind, placebo controlled, prospective study was performed in 40 children. Twenty one of them received mepiphylline in dose of 8 mg/kg/día divided in 3 during 10 days, and 19 (control group) received placebo. Salbutamol aerosols were available in both groups. Clinical and spirometric data were collected before the beginning of the treatment (pre-and-post-nebulized salbutamol), and at the 3rd, 7th and 10th days. Children and parents cooperated with a diary of symptoms, peak-flow measurements and account of salbutamol used. A total relief of symptoms was found in 14 patients in the mepiphylline group and just 8 of the control group, with no significant differences. Neither spirometry nor diary data showed significant differences. Salbutamol was less than 3 days of unnecessary in 13 patients (61.9%) in the mepiphylline group and 8 patients (42.1%) in the control group (p < 0.05; Kolmogorov-Smirnov two samples Test). We conclude that mepiphylline could be a complementary treatment of mild and moderate acute asthma with a good safety in children.

Randomized, double-blind, parallel groups, placebo-controlled study of efficacy and safety of Rynatan in the treatment of allergic rhinitis using an acute model.

We conducted a randomized, double-blind, parallel groups, placebo-controlled acute study of Rynatan (8 mg chlorpheniramine tannate, 25 mg pyrilamine tannate, 25 mg phenylephrine tannate) in 104 volunteers with allergic rhinitis. Subjects reported to City Park on a Saturday morning during the height of the grass pollen season in late spring and remained in the park for eight hours that day and on the following day. Cards were completed hourly to evaluate symptoms of allergic rhinitis and adverse experiences caused by therapy. The first three cards completed on Saturday morning were used to demonstrate that each subject had had at least minimal symptoms of allergic rhinitis and to determine baseline symptoms. Rynatan or placebo was given at noon and 7:30 PM that day and at 8:30 AM the next day. Subjects completed symptom cards hourly until 4:30 PM on Saturday, three cards that evening, and eight cards hourly the next day until 4:30 PM. The group receiving Rynatan had significantly more allergic rhinitis symptom relief than the placebo group (P = .003). More subjects in the Rynatan group (34/52) reported global symptom improvement than did subjects in the placebo group (18/52, P = .002). There were no significant severe adverse experiences and no statistically significant differences between treatment groups in incidence or severity of drowsiness, dizziness, jitteriness, headache, or nausea. We conclude that Rynatan is safe and effective in treating acute symptoms of allergic rhinitis in otherwise healthy adult subjects.

Toxic encephalopathy related to antihistamine-barbiturate antiemetic medication.

A toxic encephalopathy characterized by depressed level of consciousness, marked irritability, and ataxia developed in seven children, 5 years of age and younger, following administration of an antiemetic combination of pentobarbital and pyrilamine maleate. Three of the seven patients were given a dosage of medication and exceeding the manufacture's recommendation. All seven patients recovered without sequelae.

Sleep aids and sedatives.

Proprietary sleep aids and sedatives can cause delirium, coma and occasionally death in children and adults. The constituents in sleep aids that significantly effect central nervous system activity are bromides, methapyrilene, pyrilamine and scopolamine (hyoscine). Constituent proportions and mixtures vary greatly at different times since manufacturers make frequent adjustments. The effects of toxicity resulting from the misuse of ethylenediamines include nausea, vomiting, blurred vision, incoordination, tremors, dry mouth, constipation and an acute poisoning syndrome. Management of adverse reactions produced by either methapyrilene or pyrilamine consists of dosage reduction or discontinuation. The acute poisoning syndrome requires implementation of general symptomatic and supportive principles.