RESUMEN
Ergotism is the long-term ergot poisoning by ingestion of rye or other grains infected with the fungus Claviceps purpurea and more recently by excessive intake of ergot drugs. It has either neuropsychiatric or vascular manifestations. In the Middle Ages, the gangrenous poisoning was known as St. Anthony's fire, after the order of the Monks of St. Anthony who were particularly skilled at treating the condition. In 1917, Prof. Arthur Stoll returned home to Switzerland from Germany, to lead the development of a new pharmaceutical department at Sandoz Chemical Company. Stoll, using the special methods of extraction learned from his work with his mentor Willstetter, started his industrial research work with ergot. He succeeded in isolating, from the ergot of rye, ergotamine as an active principle of an old popular remedy for excessive post-partum bleeding. The success of this discovery occurred in 1918 and was translated into a pharmaceutical product in 1921 under the trade name Gynergen. In subsequent work, Stoll and his team were leaders in identifying the structure of the many other alkaloids and amines produced by Claviceps purpurea This was the cultural background and scientific foundation on which bromocriptine was discovered.
Asunto(s)
Antiparkinsonianos/uso terapéutico , Bromocriptina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Descubrimiento de Drogas/historia , Enfermedad de Parkinson/tratamiento farmacológico , Acromegalia/tratamiento farmacológico , Acromegalia/historia , Animales , Aniversarios y Eventos Especiales , Antiparkinsonianos/historia , Antiparkinsonianos/aislamiento & purificación , Antiparkinsonianos/envenenamiento , Bromocriptina/aislamiento & purificación , Bromocriptina/metabolismo , Bromocriptina/envenenamiento , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/historia , Agonistas de Dopamina/historia , Agonistas de Dopamina/aislamiento & purificación , Agonistas de Dopamina/envenenamiento , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/historia , Ergotismo/etiología , Ergotismo/historia , Historia del Siglo XX , Antagonistas de Hormonas/efectos adversos , Antagonistas de Hormonas/historia , Antagonistas de Hormonas/uso terapéutico , Humanos , Hiperprolactinemia/tratamiento farmacológico , Hiperprolactinemia/historia , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/historia , Hipoglucemiantes/uso terapéutico , Enfermedad de Parkinson/historia , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/historiaAsunto(s)
Antagonistas de Hormonas , Receptores de Progesterona/agonistas , Receptores de Progesterona/antagonistas & inhibidores , Animales , Historia del Siglo XX , Antagonistas de Hormonas/historia , Antagonistas de Hormonas/farmacología , Antagonistas de Hormonas/uso terapéutico , Humanos , Progesterona/historia , Receptores de Progesterona/historia , Terminología como AsuntoRESUMEN
BACKGROUND: Antiprogestins, agents that inhibit the action of progesterone, are among the most controversial and yet the more interesting therapeutic compounds developed over the past 20 years. MATERIAL AND METHODS: We present a review of the literature identified through limited searches on Medline, Cochrane and the Internet, with a discussion of the biological, clinical, political and ethical aspects of this important drug. RESULTS: The first effective antiprogestin in clinical use was mifepristone (also known as RU 486). This agent provides the most effective and safest means of medical abortion. It may also be used as a contraceptive and delivery-inducing agent and in the treatment of spontaneous abortion, ectopic pregnancies, leiomyoma, endometriosis, intrauterine fetal death, Cushing's syndrome and progesterone-dependent malignancies. INTERPRETATION: The introduction of mifepristone as an abortion-inducing agent has created intense political, ethical and moral controversies which have delayed clinical investigations and evaluations for potential expanded use.
Asunto(s)
Abortivos Esteroideos , Anticonceptivos Sintéticos Orales , Antagonistas de Hormonas , Mifepristona , Abortivos Esteroideos/administración & dosificación , Abortivos Esteroideos/química , Abortivos Esteroideos/historia , Anticonceptivos Sintéticos Orales/administración & dosificación , Anticonceptivos Sintéticos Orales/historia , Femenino , Enfermedades de los Genitales Femeninos/tratamiento farmacológico , Historia del Siglo XX , Antagonistas de Hormonas/administración & dosificación , Antagonistas de Hormonas/historia , Humanos , Trabajo de Parto Inducido , Mifepristona/administración & dosificación , Mifepristona/química , Mifepristona/historia , Neoplasias/tratamiento farmacológico , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Receptores de Progesterona/efectos de los fármacosAsunto(s)
Antineoplásicos Hormonales/historia , Neoplasias de la Mama/historia , Antagonistas de Hormonas/historia , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/terapia , Femenino , Historia del Siglo XIX , Historia del Siglo XX , Antagonistas de Hormonas/uso terapéutico , HumanosRESUMEN
The discovery of RU486 and its potent activity as an antiglucocorticoid and antiprogestin brought the long story on steroid hormones and antihormones to its logical conclusion. Even though scattered improvements are still possible, the armamentarium of the steroid endocrinologist is by now complete. Like any successful drug, RU486 has become the prototype of a number of analogues which are claimed to be either more active or more dissociated. The literature (mainly patients) has been searched for available data on abortive activities, and some as yet unpublished results on RU compounds have been included. It appears that a number of compounds are both more active than RU486 on a dose basis in animal studies and more dissociated in relation to a possible antiglucocorticoid activity. In addition, hydrosoluble compounds suitable for i.v. injection are available for possible development. In a longer term perspective, it cannot be excluded that potential non-steroidal antiprogestins could present additional advantages over steroidal compounds, in particular improved receptor specificity and/or reduced susceptibility to receptor mutation.
PIP: The discovery of RU-486 and its potent activity as an antiglucocorticoid and antiprogestin have brought the protracted story on steroid hormones and antihormones to a logical conclusion. For each of the five traditional classes of steroid hormones, estrogens, androgens, progestins, glucocorticoids, and mineralcorticoids, potent agonists and antagonists are available. The armamentarium of the steroid endocrinologist is therefore complete although scattered improvements do remain possible. RU-486 has already become the prototype of a number of analogs claimed to be either more active or more dissociated. The authors searched the literature for available data on abortive activities, including some as yet unpublished results on RU compounds. It appears that a number of compounds are both more active than RU-486 on a dose basis in animal studies and more dissociated in relation to a possible antiglucocorticoid activity. Moreover, hydrosoluble compounds suitable for IV injection are available for possible development. Over the long-term, it is possible that nonsteroidal antiprogestins may present additional advantages over steroidal compounds, in particular improved receptor specificity and/or reduced susceptibility to receptor mutation.