8/22/2019 Clase15. Neuroactive Compounds

1/39

8/22/2019 Clase15. Neuroactive Compounds

2/39

8/22/2019 Clase15. Neuroactive Compounds

3/39

Sistema Nervioso Central

8/22/2019 Clase15. Neuroactive Compounds

4/39

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

8/22/2019 Clase15. Neuroactive Compounds

5/39

8/22/2019 Clase15. Neuroactive Compounds

6/39

Alcaloides del Opio

8/22/2019 Clase15. Neuroactive Compounds

7/39

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.

8/22/2019 Clase15. Neuroactive Compounds

8/39

8/22/2019 Clase15. Neuroactive Compounds

9/39

8/22/2019 Clase15. Neuroactive Compounds

10/39

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

8/22/2019 Clase15. Neuroactive Compounds

11/39

Claviceps purpurea

8/22/2019 Clase15. Neuroactive Compounds

12/39

Huperzia serrata

8/22/2019 Clase15. Neuroactive Compounds

13/39

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.

8/22/2019 Clase15. Neuroactive Compounds

14/39

8/22/2019 Clase15. Neuroactive Compounds

15/39

8/22/2019 Clase15. Neuroactive Compounds

16/39

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.

8/22/2019 Clase15. Neuroactive Compounds

17/39

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.

8/22/2019 Clase15. Neuroactive Compounds

18/39

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.

8/22/2019 Clase15. Neuroactive Compounds

19/39

8/22/2019 Clase15. Neuroactive Compounds

20/39

8/22/2019 Clase15. Neuroactive Compounds

21/39

8/22/2019 Clase15. Neuroactive Compounds

22/39

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

Abusers onaverage reportfeeling a surge ofgratifyingsensation.

8/22/2019 Clase15. Neuroactive Compounds

23/39

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.

8/22/2019 Clase15. Neuroactive Compounds

24/39

8/22/2019 Clase15. Neuroactive Compounds

25/39

8/22/2019 Clase15. Neuroactive Compounds

26/39

8/22/2019 Clase15. Neuroactive Compounds

27/39

8/22/2019 Clase15. Neuroactive Compounds

28/39

8/22/2019 Clase15. Neuroactive Compounds

29/39

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

8/22/2019 Clase15. Neuroactive Compounds

30/39

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

8/22/2019 Clase15. Neuroactive Compounds

31/39

8/22/2019 Clase15. Neuroactive Compounds

32/39

8/22/2019 Clase15. Neuroactive Compounds

33/39

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.

8/22/2019 Clase15. Neuroactive Compounds

34/39

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

8/22/2019 Clase15. Neuroactive Compounds

35/39

8/22/2019 Clase15. Neuroactive Compounds

36/39

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:

8/22/2019 Clase15. Neuroactive Compounds

37/39

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)

8/22/2019 Clase15. Neuroactive Compounds

38/39

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.

8/22/2019 Clase15. Neuroactive Compounds

39/39