Clase15. Neuroactive Compounds

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    Sistema Nervioso Central

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    http://www.general-anaesthesia.com/images/alexander-wood.html
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    Alcaloides del Opio

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    Current Medicinal Uses and

    Purposes: The synthetic AlzheimersDisease drug Exelon is based on thephysostigmine molecule and actions.Pyridostigmine and neostigmine, both usedin the treatment of myasthenia gravis, arecousins of physostigmine.

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    Papaver somniferum is a self-sowingannual, commonly known as the 'OpiumPoppy'.

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    Claviceps purpurea

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    Huperzia serrata

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    brain degeneration, cognitive

    impairment and disturbing behavioral

    and psychiatric problems whichcharacterize the disease

    Is a progressive degeneration of brain tissue

    that primarily strikes people over age 65. It isthe most common cause of dementia in this agegroup and is marked by a devastating mentaldecline. Intellectual functions such as memory,comprehension and speech deteriorate.

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    TetrahidrocanabinolesEl THC, como principal componente psicoactivo del

    cannabis, posee todas las propiedadescaracterizadas para las drogas de abuso.

    Es capaz de activar el sistema de recompensa,

    incrementando la liberacin de dopamina, la

    principal estacin de procesamiento del aprendizaje

    asociativo mediado por experiencias placenteras.

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    Los cannabinoides son substancias que tienen una estructura carboxlicacon veintin carbonos y estn formados por tres anillos, ciclohexano,tetrahidropirano y benceno. Los principales cannabinoides son el D9-tetrahidrocannabinol (D9-THC), el D8-tetrahidrocannabinol (D8-THC), el

    cannabidiol (CBD) y el cannabinol (CBN).

    Otros cannabinoides presentes enla planta aparecen en cantidades

    diferentes segn la variedad deCannabis .El cido cannabidilico, que tieneactividad antibitica, es unconstituyente del camo.

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    El principal compuesto psicoactivo de la mariguana y el de mayorpotencia es el D9-THC. ste presenta propiedades hidrofbicas, por lo quees muy soluble en lpidos.

    Esto hace que su distribucin en el organismo y su eliminacin presentendiferencias con respecto a lo descrito para otras drogas de abuso.

    El D8-THC tiene un perfil farmacolgico muy parecido al del D9-THC,aunque sus efectos son ms dbiles; slo aparece en algunas variedades

    de la planta y su concentracin es pequea en comparacin con la del D9-THC.

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    Heroin crosses theblood-brain barrierquickly afteradministered. Inthe brain, heroin isconverted tomorphine andbinds swiftly toopioid receptors.

    Abusers onaverage reportfeeling a surge ofgratifyingsensation.

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    Aspergi l lus all iaceus-This species is not commonly reported

    from nature and is not considered common to indoorenvironments.

    It has been

    isolated from

    soils in desert

    areas,

    grassland or

    cultivated

    soils, cacti,

    onion, and

    garlic bulbs.This fungus

    should be

    considered

    allergenic.

    No toxic or

    invasive

    diseaseshave been

    documented

    to date.

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    therapeutic index/ therapeutic

    ratio The therapeutic index (also known as therapeutic

    ratio), is a comparison of the amount of a therapeuticagent that causes the therapeutic effect to the amountthat causes toxic effects.

    Quantitatively, it is the ratio given by the toxic dosedivided by the therapeutic dose.

    A commonly used measure of therapeutic index is thetoxic dose of a drug for 50% of the population (TD50)divided by the minimum effective dose for 50% of thepopulation (ED50).

    A high therapeutic index is preferable to a low one: this

    corresponds to a situation in which one would have totake a much higher amount of a drug to do harm than theamount taken to do good.

    http://en.wikipedia.org/wiki/LD50http://en.wikipedia.org/wiki/ED-50http://en.wikipedia.org/wiki/ED-50http://en.wikipedia.org/wiki/ED-50http://en.wikipedia.org/wiki/LD50http://en.wikipedia.org/wiki/LD50
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    Ejemplo.The therapeutic index for diazepam issomewhat forgiving, about = 100.

    Other drugs, however are much less so, suchas Digoxin, which has an index of 2 or 3.

    http://en.wikipedia.org/wiki/Diazepamhttp://en.wikipedia.org/wiki/Digoxinhttp://en.wikipedia.org/wiki/Digoxinhttp://en.wikipedia.org/wiki/Diazepam
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    Como resultado de una intensa bsqueda de antibiticos en muestras desuelos, Duggardescubri, en 1948, a partir de un cultivo de Streptomycesaureofaciens, la primera tetraciclina, la clorotetraciclina (aureomicina).Posteriormente, a partir de un mutante de este se obtuvo la

    demeclociclina.

    Dos aos despus (1950), Finlay y otros aislaron de un cultivo deStreptomyces rimosus, la oxitetraciclina (terramicina) y ms adelante(1953) Minieriy otros obtuvieron la tetraciclina base a partir de cepas de

    Strepmyces alboniger o texasi.Estas tetraciclinas naturales, obtenidas a partir de cepas de Strepmices,son las tetraciclinas de primera generacin.

    Una serie de nuevos compuestos semisintticos, obtenidos a partir de losanteriores, presentan mayor liposolubilidad y vida media, as como mejor

    absorcin intestinal, estas son clasificadas como tetraciclinas desegunda generacin. Entre las cuales se encuentran la doxiciclina y laminociclina.

    Por ltimo, los ms recientes y potentes componentes de esta familia, lasglicilciclinas (tigeciclina, TGB-MINO, WAY 152,288), son consideradas lastetraciclinas de tercera generacin.

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    Clasificacin por generaciones

    Tetraciclinas de primera

    generacinOral ParenteralClortetraciclina OxitetraciclinaOxitetraciclina OxitetraciclinaTetraciclina Tetraciclina

    Tetraciclinas de segundageneracin

    Oral ParenteralLimeciclina RolitetraciclinaGuameciclina LimeciclinaMepiciclina GuameciclinaTerramicina DoxiciclinaGuameciclina MinociclinaEtamociclinaClomociclinaDemeclociclinaMetaciclinaPenimociclinaTiaciclinaDoxiciclina

    Minociclina

    Tetraciclinas detercerageneracin

    Parenteral

    TigeciclinaWAY 152,288

    TGB-MINO

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    Prodrug?? Prodrugs are inactive derivatives of a drugmolecule that require a chemical or enzymatic

    biotransformation in order to release the activeparent drug in the body.

    Prodrug-technology can be applied to improvethe physicochemical, biopharmaceutical and/orpharmacokinetical properties of various drugs. Ingeneral, prodrugs are designed:

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    1. to improve the penetration of a drug across biologicalmembranes => improved drug absorption

    2. to prolong duration of action of a drug (slow release of the

    parent drug from a prodrug, decreased first-passmetabolism of the drug)3. to target the drug action (e.g. brain or tumor targeting)4. to improve aqueous solubility of a drug (i.v. preparations,

    eyedrops, etc.)5. to increase dissolution rate of a drug6. to improve topical drug delivery (e.g. dermal and ocular

    drug delivery)

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    Cyclosporine is used to treat immune-mediated diseases, especially those involving the bloodor skin.

    For treatment of anal fistulas in dogs and asthma in cats. Cyclosporine works by suppressingthe immune system. Cyclosporine (modified) has increased bioavailability compared to the

    Sandimmune brand of cyclosporine.

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