Exploratory study about the prescription pattern of medicines containing Hypericum perforatum extracts by psychiatrists in Porto Alegre (Brazil)

Neste trabalho foi realizado um estudo exploratório sobre o padrão de prescrição de medicamentos a base de Hypericum perforatum por médicos psiquiatras na cidade de Porto Alegre - RS. O desenho foi um estudo transversal, exploratório, por meio de entrevista semi-estruturada. Dos 37 psiquiatras entrevistados apenas 2 prescrevem estes medicamentos, para o tratamento de depressão leve e moderada, quando seus pacientes apresentam intolerância aos antidepressivos sintéticos. Eles consideram os resultados terapêuticos de regulares a bons e os efeitos adversos, de leves a inexistentes. A maioria dos médicos relata que tem conhecimento da utilização de H. perforatum em casos de depressão leve a moderada, principalmente através de artigos científicos e livros. A suposição de que estes produtos são pouco eficazes é a principal justificativa para sua não prescrição. Os resultados indicam que os psiquiatras conhecem medicamentos à base de H. perforatum, mas que a prescrição dos mesmos não é usual.The aim of this study was to assess the prescription pattern of medicines containing Hypericum perforatum extracts by psychiatrists in Porto Alegre ? RS. It constituted a transversal, investigational study performed by using a structured interview. The most of the interviewed physicians (37) do not prescribe medicines containing extracts of Hypericum perforatum, because they don?t believe these products are effective and safe. However they declared to have knowledge about the use of Hypericum for treating mild to moderate depression by reading scientific papers and biomedical books. Two psychiatrists informed they prescribe these medicines when the patients can?t bear the adverse effects of the standard antidepressants. They have considered the therapeutic outcome as regular to good, and did not observe significant adverse reactions. The results indicate the psychiatrists have knowledge about the use of medicines containing extracts of Hypericum perforatum as antidepressants. Nevertheless, the prescription is not common.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of pharmacological interactions of uliginosin B, a natural phloroglucinol derivative, with amitriptyline, clonidine and morphine by isobolographic analysis

AbstractUliginosin B is a natural phloroglucinol derivative, obtained from Hypericum species native to South America. Previous studies have shown that uliginosin B presents antidepressant-like and antinociceptive effects. Although its mechanism of action is still not completely elucidated, it is known that it involves the activation of monoaminergic neurotransmission. The aim of the current study was to further investigate the antinociceptive mechanism of action of uliginosin B by combining it with different drugs used for treating pain in clinical practice. The intraperitoneal administration of uliginosin B, morphine, amitriptyline and clonidine, alone or in mixture, produced a dose-dependent antinociceptive effect in the hot-plate assay in mice. The effect of the mixtures of drugs was studied using an adapted isobologram analysis at the effect level of 50% of the maximal effect observed. The analysis showed that the interactions between uliginosin B and morphine was synergistic, while the interactions between uliginosin B and amitriptyline or clonidine were additive. These findings point to uliginosin B as a potential adjuvant for pain pharmacotherapy, especially for opioid analgesia

Antidepressant-like effect of Valeriana glechomifolia Meyer (Valerianaceae) in mice

AbstractThe antidepressant-like effect of a supercritical CO2 (SCCO2) Valeriana glechomifolia extract enriched in valepotriates was investigated in a mice tail suspension test (TST) and forced swimming test (FST). The SCCO2 extract decreased mice immobility in the FST (0.5–20mg/kg p.o.) and elicited a biphasic dose–response relationship in the TST (1–20mg/kg p.o.) with no alterations in locomotor activity and motor coordination (assessed in the open-field and rota-rod tests, respectively). The anti-immobility effect of the SCCO2 extract (5mg/kg, p.o.) was prevented by mice pre-treatment with yohimbine (1mg/kg, i.p., an α2 adrenoceptor antagonist), SCH 23390 (15μg/kg, s.c., D1 dopamine receptor antagonist) and sulpiride (50mg/kg, i.p., D2 dopamine receptor antagonist). However, mice pre-treatments with prazosin (1mg/kg, i.p., α1 adrenoceptor antagonist) and p-chlorophenilalanine methyl ester (4×100mg/kg/day, i.p., a serotonin synthesis inhibitor) were not able to block the anti-immobility effect of the SCCO2 extract. Administration (p.o.) of the SCCO2 extract (0.25mg/kg) and imipramine (10mg/kg), desipramine (5mg/kg) and bupropion (3mg/kg) at sub-effective doses significantly reduced mice immobility time in the FST. These data provide the first evidence of the antidepressant-like activity of V. glechomifolia valepotriates, which is due to an interaction with dopaminergic and noradrenergic neurotransmission

Uliginosin B, a natural phloroglucinol derivative with antidepressant-like activity, increases Na+,K+-ATPase activity in mice cerebral cortex

AbstractUliginosin B, a phloroglucinol isolated from Hypericum polyanthemum Klotzsch ex Reichardt, Hypericaceae, has antidepressant-like effect in the forced swimming test in rodents and inhibits monoamines neuronal reuptake without binding to their neuronal carriers. Studies showed the involvement of Na+,K+-ATPase brain activity in depressive disorders, as well as the dependence of neuronal monoamine transport from Na+ gradient generated by Na+,K+-ATPase. This study aimed at evaluating the effect of uliginosin B on Na+,K+-ATPase activity in mice cerebral cortex and hippocampus (1 and 3h after the last administration) as well as the influence of veratrine, a Na+ channel opener, on the antidepressant-like effect of uliginosin B. Mice were treated (p.o.) with uliginosin B single (10mg/kg) or repeated doses (10mg/kg/day, 3 days). Acute administration reduced the immobility in the forced swimming test and tail suspension test and increased Na+,K+-ATPase activity in cerebral cortex 1h after treating, whereas the repeated treatment induced the antidepressant-like effect and increased the Na+,K+-ATPase activity at both times evaluated. None treatment affected the hippocampus enzyme activity. Veratrine pretreatment prevented uliginosin B antidepressant-like effect in the forced swimming test, suggesting the involvement of Na+ balance regulation on this effect. Altogether, these data indicate that uliginosin B reduces the monoamine uptake by altering Na+ gradient

Transposition methods of doses obtained from pre-clinical pharmacology for phase 1 clinical trials: Antipsicotics like study of case

Os métodos utilizados para cálculo da dose inicial em ensaios clínicos fase 1 foram revisados e aplicados ao derivado N-fenilpiperazínico LASSBio-579, candidato a antipsicótico, e aos antipsicóticos clorpromazina, clozapina, haloperidol e aripiprazol. Os métodos utilizam parâmetros toxicológicos e parâmetros farmacológicos, como a maior dose não tóxica em animais (NOAEL) ou doses ativas em animais, respectivamente. Com base no NOAEL (discrasia sanguínea e catatonia em ratos e camundongos), a dose inicial para LASSBio-579 seria 3 mg e máxima, 37,5 mg. Com base nas doses ativas (modelo de escalada induzida por apomorfina em camundongos), a dose inicial para LASSBio-579 ficaria entre 7,0-70,0 mg. Esta variação de doses também foi observada para os antipsicóticos de mercado. O método que mais se aproximou das doses terapêuticas foi o de Kuhlman (1997), baseado em doses ativas em animais.The methods used to calculate the initial dose for phase 1 clinical trials were reviewed and applied to LASSBio-579, an N-phenylpiperazine derivative antipsychotic lead, and antipsychotic drugs: chlorpromazine, clozapine, haloperidol and aripiprazole. The methods use toxicological and pharmacological parameters, such as the highest non toxic dose in animals (NOAEL) and effective dose. Based on NOAEL (induction of extrapyramidal effects and blood discrasia) in rodents, the first dose of LASSBio-579 would be 3 mg and the maximum 37.5 mg. Based on active doses (apomorphine-induced climbing), the first dose of LASSBio-579 would be in the range 7-70 mg. This large variation was also observed for the antipsychotic drugs on the market, where the method that most closely approximated the doses used in therapy was the Kuhlman method (1997), based on active doses.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Survey of plants popularly used for pain relief in Rio Grande do Sul, southern Brazil

Ethnobotanical data can be an important tool in the search for new drugs. The Brazilian Health Surveillance Agency accepts the registration of herbal medicines based on ethnopharmacological and ethnobotanical studies. With the purpose of increasing the knowledge of potentially useful plants for the treatment of painful conditions, we analyzed the ethnobotanical studies carried out in Rio Grande do Sul state (RS-Southern Brazil); we had access to nineteen studies. To our knowledge, this is the first compilation of ethnobotanical studies that focus on pain relief carried out in RS. The species native to RS cited in at least nine (about 50%) of these studies were selected. The search retrieved 28 native species cited as used to alleviate painful conditions, which are distributed in eighteen botanical families, being Asteraceae the most mentioned. The species more frequently cited for pain relief were Achyrocline satureioides, Baccharis articulata, Baccharis crispa, Lepidium didymum, Eugenia uniflora and Maytenus ilicifolia. The only species not reported in any pre-clinical study associated with pain relief was B. articulata. Among the six species cited, no studies on clinical efficacy were found. In conclusion, the folk use of native plants with therapeutic purposes is widespread in RS State (Brazil), being pain relief an important property. Keywords: Ethnobotany, Folk medicine, Pain, South Brazi

Uliginosin B presents antinociceptive effect mediated by dopaminergic and opioid systems in mice

AbstractPrevious studies have shown that uliginosin B inhibits dopamine reuptake in rat brain. This compound occurs in Hypericum polyanthemum and H. caprifoliatum for which was reported to have antinociceptive effect sensitive to naloxone. The aim of this study was to assess the antinociceptive effect of uliginosin B and to evaluate the involvement of opioid and dopaminergic receptors activation. Uliginosin B presented antinociceptive effect in hot-plate and abdominal writhing tests, in mice, at doses that did not impair the motor coordination (15mg/kg, i.p.). Uliginosin B in high dose (90mg/kg, i.p.) presented ataxic effect in the rotarod apparatus. These effects seem to be mediated by distinct receptors since the effect on the hot-plate was completely abolished by naloxone and sulpiride, but it was unaffected by SCH 23390. On the other hand, the motor impairment induced by uliginosin B was completely prevented by naloxone and partially prevented by sulpiride and SCH 23390. However, the receptors' activation appears to be indirect since uliginosin B did not bind to opioid and dopaminergic receptors. Thus, uliginosin B effects probably are due to its ability to inhibit monoamine reuptake with consequent activation of dopamine receptors and indirect stimulation of opioid system

Participation of GABA-benzodiazepine Receptor Complex in the Anxiolytic Effect of Passiflora alata Curtis (Passifloraceae)

Passiflora alata Curtis is used in Brazilian folk medicine and also by pharmaceutical industry due to its tranquilizing properties. In this work, the central activity of an aqueous (AQ) and an hydroethanolic (HE) leaves extracts were evaluated in elevated plus maze, barbiturate sleeping time, open field and [3H]flunitrazepam binding assays. The only effect presented by AQ (300 mg/kg, p.o.) was on the barbiturate sleeping time, indicating a hypnotic effect. The HE extract (300 and 600 mg/kg, p.o.) also increased the barbiturate sleeping time and reduced the locomotor activity (at 600 mg/kg, p.o.), pointing to a sedative effect. In addition HE showed an anxiolytic-like effect (300 mg/kg, p.o.) in the elevated plus maze test which was blocked by flumazenil (6 mg/kg, i.p.). Nevertheless HE did not displace [3H]flunitrazepam binding to rat brain synaptosomes in concentrations up to 1000 μg/mL. As a conclusion, we showed that the anxiolytic effect of P. alata in mice depends on the dose and solvent used for the extract preparation, and this effect cannot be attributed to the direct activation of the central benzodiazepine site by the chemical constituents of the extract. It is possible that their metabolites or an indirect effect on benzodiazepine- GABAA receptor complex mediate the observed anxiolytic effect.Colegio de Farmacéuticos de la Provincia de Buenos Aire