RESUMEN
Pain remains a very pervasive problem throughout medicine. Classical pain management is achieved through the use of opiates belonging to the mu opioid receptor (MOR) class, which have significant side effects that hinder their utility. Pharmacologists have been trying to develop opioids devoid of side effects since the isolation of morphine from papaver somniferum, more commonly known as opium by Sertürner in 1804. The natural products salvinorin A, mitragynine, and collybolide represent three nonmorphinan natural product-based targets, which are potent selective agonists of opioid receptors, and emerging next-generation analgesics. In this work, we review the phytochemistry and medicinal chemistry efforts on these templates and their effects on affinity, selectivity, analgesic actions, and a myriad of other opioid-receptor-related behavioral effects.
Asunto(s)
Productos Biológicos/farmacología , Diterpenos de Tipo Clerodano/farmacología , Dolor/tratamiento farmacológico , Alcaloides de Triptamina Secologanina/farmacología , Animales , Productos Biológicos/química , Productos Biológicos/uso terapéutico , Diterpenos de Tipo Clerodano/química , Diterpenos de Tipo Clerodano/uso terapéutico , Humanos , Fitoterapia , Alcaloides de Triptamina Secologanina/química , Alcaloides de Triptamina Secologanina/uso terapéuticoRESUMEN
Kratom (Mitragyna speciosa) is a tree-like plant indigenous to Southeast Asia. Its leaves, and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. Evidence suggests kratom is being increasingly used by people in the United States and Europe for the self-management of opioid withdrawal and treatment of pain. Recent studies have confirmed that kratom and its chemical constituents have potentially useful pharmacological actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule I Controlled Substances, a move that triggered a massive response from pro-kratom advocates. The debate regarding the risks, and benefits and safety of kratom continues to intensify. Kratom proponents tout kratom as a safer and less addictive alternative to opioids for the management of pain and opioid addiction. The anti-kratom faction argues that kratom, itself, is a dangerous and addictive drug that ought to be banned. Given the widespread use of kratom and the extensive media attention it is receiving, it is important for physicians, scientists and policy makers to be knowledgeable about the subject. The purpose of this commentary is to update readers about recent developments and controversies in this rapidly evolving area. All of the authors are engaged in various aspects of kratom research and it is our intention to provide a fair and balanced overview that can form the basis for informed decisions on kratom policy. Our conclusions from these analyses are: (a) User reports and results of preclinical studies in animals strongly suggest that kratom and its main constituent alkaloid, mitragynine may have useful activity in alleviating pain and managing symptoms of opioid withdrawal, even though well-controlled clinical trials have yet to be done. (b) Even though kratom lacks many of the toxicities of classic opioids, there are legitimate concerns about the safety and lack of quality control of purported "kratom" products that are being sold in the US. (c) The issues regarding the safety and efficacy of kratom and its mitragynine constituent can only be resolved by additional research. Classification of the Mitragyna alkaloids as Schedule I controlled substances would substantially impede this important research on kratom.
Asunto(s)
Control de Medicamentos y Narcóticos/legislación & jurisprudencia , Mitragyna/efectos adversos , Extractos Vegetales/efectos adversos , Extractos Vegetales/uso terapéutico , Alcaloides de Triptamina Secologanina/efectos adversos , Animales , Humanos , Extractos Vegetales/farmacología , Hojas de la Planta/efectos adversos , Alcaloides de Triptamina Secologanina/farmacología , Alcaloides de Triptamina Secologanina/uso terapéutico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) Havil. (M. speciosa) is among the most well-known plants used in ethnic practice of Southeast Asia. It has gained increasing attention as a plant with potential to substitute morphine in addiction treatment program. However, its action on the central nervous system is controversial. AIM OF THE STUDY: This study investigated the effects of M. speciosa alkaloid extract on naloxone-precipitated morphine withdrawal and neural signaling in the nucleus accumbens (NAc, brain reward center) of mice. MATERIALS AND METHODS: The effects of M. speciosa alkaloid extract and mitragynine, a pure major constituent, on naloxone-precipitated morphine withdrawal were examined. Male Swiss Albino (ICR) mice were rendered dependent on morphine before injection with naloxone, a nonspecific opioid antagonist, to induce morphine withdrawal symptoms. The intensity of naloxone-precipitated morphine withdrawal was assessed from jumping behavior and diarrhea induced during a period of morphine withdrawal. To test possible addictive effect of M. speciosa alkaloid extract, mice were implanted with intracranial electrode into the NAc for local field potential (LFP) recording. Following M. speciosa alkaloid extract (80mg/kg) and morphine (15mg/kg) treatment, LFP power spectra and spontaneous motor activity were analyzed in comparison to control levels. RESULTS: One-way ANOVA and multiple comparisons revealed that M. speciosa alkaloid extract (80 and 100mg/kg) significantly decreased the number of jumping behavior induced by morphine withdrawal whereas mitragynine did not. Additionally, M. speciosa alkaloid extract significantly decreased dry and wet fecal excretions induced by morphine withdrawal. LFP analysis revealed that morphine significantly decreased alpha (9.7-12Hz) and increased low gamma (30.3-44.9Hz) and high gamma (60.5-95.7Hz) powers in the NAc whereas M. speciosa alkaloid extract did not. Spontaneous motor activity was significantly increased by morphine but not M. speciosa alkaloid extract. CONCLUSIONS: Taken together, M. speciosa alkaloid extract, but not mitragynine, attenuated the severity of naloxone-precipitated morphine withdrawal symptoms. Neural signaling in the NAc and spontaneous motor activity were sensitive to morphine but not M. speciosa alkaloid extract. Therefore, treatment with the M. speciosa alkaloid extract may be useful for opiate addiction treatment program.
Asunto(s)
Alcaloides/uso terapéutico , Analgésicos Opioides , Mitragyna , Morfina , Extractos Vegetales/uso terapéutico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Animales , Conducta Animal/efectos de los fármacos , Diarrea/tratamiento farmacológico , Masculino , Ratones Endogámicos ICR , Naloxona , Antagonistas de Narcóticos , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/fisiología , Hojas de la Planta , Alcaloides de Triptamina Secologanina/uso terapéutico , Síndrome de Abstinencia a Sustancias/etiologíaRESUMEN
OBJECTIVE: Kratom (Mitragyna speciosa. Korth) is an indigenous medicinal plant of Southeast Asia. This review paper aims to describe the trends of kratom use in Southeast Asia. DESIGN: A literature review search was conducted through ScienceDirect, Scopus, ProMed and Google Scholar. Twenty-five articles illustrating kratom use in humans in Southeast Asia were reviewed. RESULTS: Kratom has long been used by rural populations in Southeast Asia as a remedy for common ailments, to fight fatigue from hard manual work, as a drink during social interaction among men, and in village religious functions. Studies based on self-reports suggest that prolonged kratom use does not result in serious health risks or impair social functioning. Two recent trends have also emerged: (a) Kratom is reportedly being used to ease withdrawal from opioid dependence in rural settings; whereas (b) in urban areas, adulterated kratom cocktails are being consumed by younger people to induce euphoria. CONCLUSIONS: Legal sanctions appear to have preceded serious scientific investigations into the claimed benefits of ketum. More objective-controlled trials and experiments on humans need to be conducted to validate self-report claims by kratom users in the community.
Asunto(s)
Mitragyna , Alcaloides de Triptamina Secologanina/efectos adversos , Alcaloides de Triptamina Secologanina/uso terapéutico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/epidemiología , Asia Sudoriental/epidemiología , Humanos , Trastornos Relacionados con Opioides/diagnóstico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Plantas Medicinales/efectos adversos , Síndrome de Abstinencia a Sustancias/diagnósticoRESUMEN
Kratom (Mitragyna speciosa) is a plant indigenous to Southeast Asia. Its leaves and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. In a comprehensive review published in 2012, Prozialeck et al presented evidence that kratom had been increasingly used for the self-management of opioid withdrawal and pain in the United States. At the time, kratom was classified as a legal herbal product by the US Drug Enforcement Administration. Recent studies have confirmed that kratom and its chemical constituents do have useful pharmacologic actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule 1 controlled substances, a move that triggered a massive response from kratom advocates. The purpose of this report is to highlight the current scientific and legal controversies regarding kratom.
Asunto(s)
Mitragyna/química , Alcaloides de Triptamina Secologanina/uso terapéutico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Analgésicos Opioides/efectos adversos , Control de Medicamentos y Narcóticos , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Manejo del Dolor/métodos , Extractos Vegetales/efectos adversos , Extractos Vegetales/uso terapéutico , Alcaloides de Triptamina Secologanina/farmacología , Autocuidado , Estados UnidosRESUMEN
(E)-Methyl 2-((2S,3S,7aS,12bS)-3-ethyl-7a-hydroxy-8-methoxy-1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate (7-hydroxymitragynine), a main active constituent of the traditional herbal medicine Mitragyna speciosa, is an indole alkaloid that is structurally different from morphine. 7-Hydroxymitragynine induces a potent antinociceptive effect on mouse acute pain through µ-opioid receptors. In this study, we developed dual-acting µ- and δ-opioid agonists MGM-15 and MGM-16 from 7-hydroxymitragynine for the treatment of acute and chronic pain. MGM-16 showed a higher potency than that of 7-hydroxymitragynine and MGM-15 in in vitro and in vivo assays. MGM-16 exhibited a high affinity for µ- and δ-opioid receptors, with K(i) values of 2.1 and 7.0 nM, respectively. MGM-16 showed µ- and δ-opioid full agonistic effects in a guanosine 5'-O-(3-[(35)S]thiotriphosphate) binding assay and in a functional test using electrically elicited guinea pig ileum and mouse vas deferens contractions. Systemic administration of MGM-16 produced antinociceptive effects in a mouse acute pain model and antiallodynic effects in a chronic pain model. The antinociceptive effect of MGM-16 was approximately 240 times more potent than that of morphine in a mouse tail-flick test, and its antiallodynic effect was approximately 100 times more potent than that of gabapentin in partial sciatic nerve-ligated mice, especially with oral administration. The antinociceptive effect of MGM-16 was completely and partially blocked by the µ-selective antagonist ß-funaltrexamine hydrochloride (ß-FNA) and by the δ-selective antagonist naltrindole, respectively, in a tail-flick test. The antiallodynic effect of MGM-16 was completely blocked by ß-FNA and naltrindole in a neuropathic pain model. These findings suggest that MGM-16 could become a class of a compound with potential therapeutic utility for treating neuropathic pain.
Asunto(s)
Hiperalgesia/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Receptores Opioides delta/agonistas , Receptores Opioides mu/agonistas , Alcaloides de Triptamina Secologanina/farmacología , Administración Oral , Animales , Células CHO , Cricetinae , Cricetulus , Hiperalgesia/fisiopatología , Íleon/efectos de los fármacos , Íleon/fisiopatología , Inyecciones Subcutáneas , Masculino , Ratones , Contracción Muscular , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Neuralgia/fisiopatología , Estimulación Física , Conejos , Ensayo de Unión Radioligante , Receptores Opioides delta/antagonistas & inhibidores , Receptores Opioides mu/antagonistas & inhibidores , Neuropatía Ciática/tratamiento farmacológico , Neuropatía Ciática/fisiopatología , Alcaloides de Triptamina Secologanina/química , Alcaloides de Triptamina Secologanina/uso terapéutico , Estereoisomerismo , Tacto , Conducto Deferente/efectos de los fármacos , Conducto Deferente/fisiopatologíaRESUMEN
Kratom (or Ketum) is a psychoactive plant preparation used in Southeast Asia. It is derived from the plant Mitragyna speciosa Korth. Kratom as well as its main alkaloid, mitragynine, currently spreads around the world. Thus, addiction potential and adverse health consequences are becoming an important issue for health authorities. Here we reviewed the available evidence and identified future research needs. It was found that mitragynine and M. speciosa preparations are systematically consumed with rather well defined instrumentalization goals, e.g. to enhance tolerance for hard work or as a substitute in the self-treatment of opiate addiction. There is also evidence from experimental animal models supporting analgesic, muscle relaxant, anti-inflammatory as well as strong anorectic effects. In humans, regular consumption may escalate, lead to tolerance and may yield aversive withdrawal effects. Mitragynine and its derivatives actions in the central nervous system involve µ-opioid receptors, neuronal Ca²âº channels and descending monoaminergic projections. Altogether, available data currently suggest both, a therapeutic as well as an abuse potential.
Asunto(s)
Analgésicos/efectos adversos , Conducta Adictiva/psicología , Sistema Nervioso Central/efectos de los fármacos , Mitragyna/efectos adversos , Alcaloides de Triptamina Secologanina/efectos adversos , Trastornos Relacionados con Sustancias/psicología , Alcaloides/química , Alcaloides/farmacología , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Asia Sudoriental , Modelos Animales de Enfermedad , Humanos , Mitragyna/química , Estructura Molecular , Extractos Vegetales/efectos adversos , Alcaloides de Triptamina Secologanina/farmacología , Alcaloides de Triptamina Secologanina/uso terapéutico , Automedicación/psicologíaRESUMEN
AIM OF THE STUDY: Since remedies for mental disorders have been sought through both orthodox and traditional medicine this study compared the effects of the antipsychotic, chlorpromazine (Cpz), the herb Rauwolfia vomitoria (RV) and its alkaloid reserpine (Res) in mice. MATERIALS AND METHODS: Ninety male CD-1 strain of mice (75-80 days old; 30-34 g body weight) were divided into 3 major groups and each consisting 5 subgroups (n=6). Cpz (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.), was administered 30 min before testing. RV (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) and Res (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p.) were administered 24 h before testing. The open field test was used to assess locomotor and exploratory behaviour, acceleratory rotarod for motor coordination, light/dark box for anxiety. RESULTS: CPZ dose-dependently decreased locomotor and exploration behaviour and impaired motor coordination (p<0.01). RV also decreased locomotor behaviour at 4.0 mg/kg (p<0.5) but did not alter exploration and motor coordination. Res however, decreased locomotion and exploration and impaired motor coordination 0.8 and 1.6 mg/kg (p<0.05). In the light/dark box, CPZ increased anxiety related behaviour at 1.0, 2.0 mg/kg (p<0.05) whereas RV dose-dependently decreased anxiety from 1.0 to 4.0 mg/kg (p<0.01). Res, unlike RV, dose-dependently increased anxiety related behaviour from 0.4 to 1.6 mg/kg. CONCLUSION: Root bark extract from Rauwolfia vomitoria produced better behavioural effects with less distortion in motor coordination when compared to chlorpromazine and so has a great potential as an alternative antipsychotic agent compared to chlorpromazine. Since Res did not produce same effects as RV, the effect of RV may not be due solely to Res as claimed.
Asunto(s)
Antipsicóticos/farmacología , Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Clorpromazina/farmacología , Actividad Motora/efectos de los fármacos , Rauwolfia/química , Animales , Antipsicóticos/uso terapéutico , Clorpromazina/uso terapéutico , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos , Corteza de la Planta/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Raíces de Plantas/química , Reserpina/aislamiento & purificación , Reserpina/farmacología , Reserpina/uso terapéutico , Prueba de Desempeño de Rotación con Aceleración Constante , Alcaloides de Triptamina Secologanina/aislamiento & purificación , Alcaloides de Triptamina Secologanina/farmacología , Alcaloides de Triptamina Secologanina/uso terapéuticoRESUMEN
Mitragynine is a major indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa that has opium-like properties, although its chemical structure is quite different from that of morphine. We attempted to develop novel analgesics derived from mitragynine, and thus synthesized the ethylene glycol-bridged and C10-fluorinated derivative of mitragynine, MGM-9 [(E)-methyl 2-(3-ethyl-7a,12a-(epoxyethanoxy)-9-fluoro-1,2,3,4,6,7,12,12b-octahydro-8-methoxyindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate]. We hypothesized that a dual-acting mu- and kappa-opioid agonist could produce potent antinociceptive effects with fewer rewarding effects compared with mu agonists. In this study, MGM-9 exhibited high affinity for mu- and kappa-opioid receptors with Ki values of 7.3 and 18 nM, respectively. MGM-9 showed a potent opioid agonistic effect, and its effects were meditated by mu- and kappa-opioid receptor mechanisms in in vitro assays. Subcutaneous and oral administration of MGM-9 produced potent antinociceptive effects in mouse tail-flick, hot-plate, and writhing tests. When administered orally, the antinociceptive effect of MGM-9 was seven to 22 times more potent than that of morphine. The antinociceptive effects of MGM-9 were mediated by both mu- and kappa-opioid receptors. Subcutaneous administration of MGM-9 twice daily for 5 days led to antinociceptive tolerance. In the gastrointestinal transit study, MGM-9 inhibited gastrointestinal transit, but its effect was weaker than that of morphine at equi-antinociceptive doses. Furthermore, MGM-9 induced less hyperlocomotion and fewer rewarding effects than morphine. The rewarding effect of MGM-9 was blocked by a mu antagonist and enhanced by a kappa antagonist. Taken together, the results suggest that MGM-9 is a promising novel analgesic that has a stronger antinociceptive effect and weaker adverse effects than morphine.
Asunto(s)
Umbral del Dolor/efectos de los fármacos , Dolor/tratamiento farmacológico , Receptores Opioides kappa/agonistas , Receptores Opioides mu/agonistas , Recompensa , Alcaloides de Triptamina Secologanina/farmacología , Analgésicos Opioides/farmacología , Análisis de Varianza , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Vías de Administración de Medicamentos , Tolerancia a Medicamentos , Tránsito Gastrointestinal/efectos de los fármacos , Cobayas , Masculino , Ratones , Morfina/uso terapéutico , Derivados de la Morfina/uso terapéutico , Dolor/clasificación , Dolor/etiología , Dimensión del Dolor/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Alcaloides de Triptamina Secologanina/química , Alcaloides de Triptamina Secologanina/uso terapéutico , Factores de TiempoRESUMEN
This study describes patterns and consequences of chewing leaves of krathom, Mitragynine speciosa, Kroth., traditionally used by rural people in Thailand as a mild narcotic. We surveyed 149 long-term regular users (daily for >or= 5 years), 168 occasional users (used only in social situations or medicinally, less than once a week), and 116 nonusers from three rural villages where krathom use was traditional in southern Thailand. Users focused on the perceived advantages of krathom in relation to increased work endurance, medication, and as a substitute for other hard substances rather than its harmful effects. Limitations regarding self-report and generalizability of the study were noted, and further longitudinal study among other population groups is required for educating people and users about possible harmful impacts of krathom use.
Asunto(s)
Alcaloides de Triptamina Secologanina/uso terapéutico , Trastornos Relacionados con Sustancias/etiología , Adolescente , Adulto , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Extractos Vegetales , Hojas de la Planta , Alcaloides de Triptamina Secologanina/administración & dosificación , TailandiaRESUMEN
Nine quinovic acid glycosides and the alkaloid cadambine acid isolated from N. diderrichii, an evergreen endemic plant of West and Central Africa, were assessed for their in vitro antileishmanial activity against Leishmania infantum. Four quinovic acid glycosides and cadambine acid revealed a strong antileishmanial activity (IC (50) = 1 microM) highly specific for the intracellular amastigote form of the parasite. Quinovic acid glycosides were shown to inhibit parasite internalisation by interfering with promastigotes while cadambine acid exerted immunomodulatory activity by inducing NO production in human macrophages. The association of cadambine acid with amphotericin B demonstrated an interesting synergism, suggesting that cadambine acid could be used as a complement of such conventional therapy.
Asunto(s)
Antiprotozoarios/farmacología , Leishmania infantum/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Rubiaceae , Animales , Antiprotozoarios/administración & dosificación , Antiprotozoarios/uso terapéutico , Glicósidos/administración & dosificación , Glicósidos/farmacología , Glicósidos/uso terapéutico , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Leishmaniasis Visceral/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Óxido Nítrico/metabolismo , Pruebas de Sensibilidad Parasitaria , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Alcaloides de Triptamina Secologanina/administración & dosificación , Alcaloides de Triptamina Secologanina/farmacología , Alcaloides de Triptamina Secologanina/uso terapéutico , Triterpenos/administración & dosificación , Triterpenos/farmacología , Triterpenos/uso terapéuticoRESUMEN
Recently, we found that mitragynine, a major constituent of Mitragyna speciosa, has an opioid agonistic activity, but its weak potency could not explain the opium-like effect of this plant. In the present study, bioassay-guided fractionation of the crude extract of the leaves of M. speciosa was carried out to search for potent opioid agonists other than mitragynine. Opioid agonistic activities were evaluated using twitch contraction induced by electrical stimulation in guinea-pig ileum. The crude extract of M. speciosa inhibited the twitch contraction in a concentration-dependent manner. The inhibition was reversed by naloxone. The opioid effect was detected only in the crude base fraction, which was followed by the isolation of five indole alkaloids. Among these alkaloids, 7-hydroxymitragynine showed the most potent opioid effect on the electrically-stimulated contraction (pD (2) = 8.38 +/- 0.12). The potency, calculated using pD (2) values, was 30- and 17-fold higher than that of mitragynine and morphine, respectively. Antagonism of naloxone on concentration-response curves for 7-hydroxymitragynine confirmed its opioid effect. These results suggest that the opioid effect of M. speciosa is mostly based on the activity of 7-hydroxymitragynine.
Asunto(s)
Analgésicos Opioides/farmacología , Mitragyna , Fitoterapia , Receptores Opioides/efectos de los fármacos , Alcaloides de Triptamina Secologanina/farmacología , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Cobayas , Íleon/efectos de los fármacos , Alcaloides Indólicos/administración & dosificación , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/uso terapéutico , Masculino , Medicina Tradicional , Contracción Muscular/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Alcaloides de Triptamina Secologanina/administración & dosificación , Alcaloides de Triptamina Secologanina/uso terapéutico , TailandiaRESUMEN
Psychiatry co-morbidity with epilepsy is common and often requires the combined use of psychotropic and antiepileptic drugs (AEDs). For schizophrenic patients, the occurrence of seizures with atypical agents is highest among antipsychotics, although these agents are more effective in alleviating symptoms (including negative symptoms) and are associated with fewer extrapiramidal effects. The indol alkaloid alstonine is the major component of plants used by traditional Nigerian psychiatrists as anti-dementia drugs. The alkaloid presents an experimental profile very similar to the atypical antipsychotic clozapine. This study aimed to compare the pro-convulsant activity of these two antipsychotic compounds. Through repetitive administration over a 30-day period in a kindling paradigm, it is shown that, unlike clozapine, alstonine does not possess pro-convulsant activity. The data adds to previous suggestions that alstonine deserves to be scrutinized as a model for the development of newer antipsychotics.
Asunto(s)
Anticonvulsivantes/farmacología , Antipsicóticos/farmacología , Apocynaceae , Fitoterapia , Alcaloides de Triptamina Secologanina/farmacología , Convulsiones/prevención & control , Animales , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Clozapina/farmacología , Masculino , Ratones , Ratones Endogámicos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Alcaloides de Triptamina Secologanina/administración & dosificación , Alcaloides de Triptamina Secologanina/uso terapéuticoAsunto(s)
Benzotiadiazinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Alcaloides de Triptamina Secologanina/uso terapéutico , Anciano , Combinación de Medicamentos , Evaluación de Medicamentos , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Extractos Vegetales/uso terapéuticoAsunto(s)
Antihipertensivos/uso terapéutico , Benzotiadiazinas , Hipertensión/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Potasio/uso terapéutico , Alcaloides de Triptamina Secologanina/uso terapéutico , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Diuréticos , Combinación de Medicamentos , Evaluación de Medicamentos , HumanosAsunto(s)
Hipertensión/terapia , Astenia Neurocirculatoria/terapia , Bencimidazoles/uso terapéutico , Quimioterapia Combinada , Terapia por Estimulación Eléctrica , Estudios de Evaluación como Asunto , Humanos , Hipertensión/complicaciones , Metildopa/uso terapéutico , Astenia Neurocirculatoria/complicaciones , Papaverina/uso terapéutico , Perfenazina/uso terapéutico , Alcaloides de Triptamina Secologanina/uso terapéuticoRESUMEN
Drugs used in the management of pregnancy-induced hypertension have been reviewed, and their value and adverse effects on both mother and fetus have been considered. Although magnesium and hydralazine remain the stalwarts of therapy, a number of other drugs have potential that may be realized in the future. Several new medications have promise in correcting the derangements of toxemia, but safety for the fetus has yet to be demonstrated. For the physician confronted with the complexities of old and new drugs in toxemia of pregnancy, the prayer of Lord Berkely may be just as appropriate in 1977 as it was dicades ago: From inability to let well enough alone, From too much zeal for the new, From too much contempt for what is old, From putting knowledge before wisdom and science before art, From making the cure of the disease more grievous than its endurnace, Good Lord, deliver us.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Antihipertensivos/uso terapéutico , Diuréticos/uso terapéutico , Preeclampsia/tratamiento farmacológico , Barbitúricos/efectos adversos , Benzotiadiazinas , Volumen Sanguíneo , Diazepam/efectos adversos , Diazepam/uso terapéutico , Ácido Etacrínico/efectos adversos , Femenino , Furosemida/efectos adversos , Furosemida/uso terapéutico , Heparina/efectos adversos , Humanos , Hidralazina/efectos adversos , Hidralazina/uso terapéutico , Magnesio/efectos adversos , Magnesio/uso terapéutico , Manitol/efectos adversos , Manitol/uso terapéutico , Metildopa/uso terapéutico , Miometrio/efectos de los fármacos , Fitoterapia , Plantas Medicinales , Plantas Tóxicas , Embarazo , Ritodrina/uso terapéutico , Alcaloides de Triptamina Secologanina/uso terapéutico , Inhibidores de los Simportadores del Cloruro de Sodio/efectos adversos , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Veratrum/uso terapéuticoRESUMEN
The aetiopathogenesis and diagnosis of Martorell's supra-malleolar hypertensive ulcer are discussed in the light of 3 clinical cases. Stress is laid on the overriding need for proper general management designed to normalise the serious arterial hypertension. It is felt that raubasine vasokinetics (such as Circolene), and taurine tissue oxygenators (0-due) are useful supplementary aids, particularly when administered by slow infusion. Lumbar gangliectomy will be necessary in the case of persistently painful ulcers. Its success, however, is dependent on prior normalisation of pressure. Dermo-epidermal grafts would appear to be superfluous, while frequent topical application of trophodermic creams are apparently useless.