Derivados lúdicos sobre los receptores NMDA.Una nueva droga: la Difenidina.

 La fórmula estructural  aquí descrita NO es la   Dienidina sino
Mk 801, estructuralmente  similar  a la Difenidina, al MO 801, una  droga usada ampliamente en Farmacología Experimental para el estudio d elos  receptores NMDA, también se la  conoce  como  Dizocilpina.

Desde el Sistema de Alerta Temprana del Observatorio Europeo de las Drogas y las Toxicomanías, nos llega información sobre la notificación, por parte de Reino Unido e Italia, de una nueva sustancia: 1-(1,2-Difeniletil)piperidina (difenidina).

Esta sustancia es una Piperidina psicodisléptica, esta palabreja ya tira de espaldas, sencillamente es una sustancia que interacciona con dichos receptores.Se trata de un bloqueante de los canales del receptor NMDA, que ha sido objeto de estudio para el tratamiento de la neurotoxicidad.

Si recordamos algo sobre éstos receptores   para aminoácidos excitadores como el glutamato , entramos en un maravilloso mundo: el de los   fármacos como la Dizocilpina o Mk 801, una sustancia agonista no competitivo  con una patente del Laboratorio Merck de 1982. para dichos receptores. 

 

Abajo vemos el mopdelos tridimensional de ésta sustancia, que pod´ria explica de forma estequiométrica la adaptacióna un posible recpetor en cerebro de éstos derivados  y su capacidad de producir dependencia, lo cual nos conduce a su posible uso lúdico.

Para no caer en el error de hacer apología de la miusma,  citamos  en  su forma original  las posibles acciones no autporizadas de la misma, en especial su capacidad de generar esquizofrenia en modelos animales.

Behavioural studies have shown that NMDA receptors are involved in the development of psychological dependence caused by chronic administration of morphine. MK-801 suppressed the morphine-induced rewarding effect. It is suggested that stimulating NR2B subunits of the NMDA receptor and its associated kinases in the nucleus accumbens leads to the rewarding effect caused by morphine. Inhibition of this receptor and its kinases in the nucleus accumbens by co-treatment with NMDA antagonists prevents morphine-associated psychological dependence.^[18] An earlier study has shown that the prevention of morphine-associated psychological dependence was not due to state-dependency effects induced by MK-801^[ but rather reflect the impairment of learning that is caused by NMDA antagonists.^] This is consistent with studies showing that MK-801 potentiates the addictive potential of morphine and other drugs (see below).

3-D molecular model

As an antidepressant, positive results ug, and may have an active dose in the 50-100 μg range. Little is known in this context about its effects, dosage, and risks. The high potency of dizocilpine makes its dosage more difficult to accurately control when compared to other similar drugs. As a result, the chances ofoverdosing are high. Users tend to report that the experience is not as enjoyable as other dissociative drugs, and it is often accompanied by strong auditory hallucinations. Also, dizocilpine is much longer-lasting than similar dissociative drugs such as ketamine and phencyclidine (PCP), and causes far worse amnesia and residual deficits in thinking, which have hindered its acceptance as a recreational drug.

 Several animal studies have demonstrated the addictive potential of dizocilpine. Rats learned to lever-press in order to obtain injections of MK-801 into the nucleus accumbens and frontal cortex, however, when given a dopamine antagonist at the same time, the lever-pressing was not altered, which shows that the rewarding effect of MK-801 is not dependent on dopamine.Intraperitoneal administration of MK-801 also produced an enhancement in self-stimulation responding.^]Rhesus monkeys were trained to self-administer cocaine or phencyclidine, then were offered MK-801 instead. None of the four monkeys who were used to cocaine chose to self-administer MK-801 but three out of the four monkeys who had been using phencyclidine self-administered MK-801, suggesting again that MK-801 has potential as a recreational drug for those seeking a dissociative anaesthetic type of experience. It was found that MK-801 administration elicited conditioned place preference in animals, again demonstrating its reinforcing properties.

Italia ha notificado la detección de Difenidina  a partir del decomiso de un envío que contenía una bolsa de plástico con 1,040 gramos de polvo blanco y que fue decomisado por la Policía en 2013.

¿Iguales, todos iguales?

 Interesante artículo en el que se determina que los ácidos grasos presentes en las huellas dactilares  tienen un perfil diferente para cada uno de nosotros.
Sus utilidades en el marco de la Medicina Forense serán dignas de  estudio en los años venideros.En vez de la clásica estampa de  mojar las yemas de los dedos en  la tinta china, me veo recogiendo con la torunda de algodón la grasilla de los dedos y pasándola por un  Cromatógrafo de Gases...

A fingermark feast

The adoption of fingerprints in the late 19th Century revolutionised the identification of criminals and they are still used extensively by virtually all law enforcement agencies today. However, recent research into fingermarks, as they are now called, has shown that they can yield much more information, revealing substances that a suspect has been in contact with, or even that they have taken into the body.
For instance, it is now generally accepted that traces of explosives and gunshot residue can be detected in latent prints by chemical and spectroscopic techniques. Smokers can be pinpointed by the presence of nicotine and its metabolite cotinine in the prints. Drugs and their metabolites can also travel through the body to emerge in fingermarks to point the finger at people who have taken illicit or prescription drugs.
Researchers at Sheffield Hallam University, UK, have shown that the gender of a person can be predicted with promising accuracy from the presence of peptides and proteins in the fingermarks. They expect that their mass spectrometric technique will be able to "provide information on traits such as nutritional habits, drug use or hormonal status."
Now, a team of researchers in the USA has used a different approach which examines the fatty acids in latent fingermarks. Preliminary results appear to show that ratios of particular fatty acids can discriminate between race and gender. Frank Dorman, Seth Michalski and Robert Shaler from the Forensic Science Program at Pennsylvania State University published details of their findings in the Journal of Forensic Sciences.
There are three glands in the human body which contribute to fingermarks. The eccrine glands, which are found all over the body but are abundant on the palms and soles, secrete a complex mixture of organic and inorganic components as well as a high proportion of water. The apocrine glands in the pubic, anal and mammary regions secrete a mixture of iron, proteins and carbohydrates.
It was the third type of gland that interested the research team. The sebaceous glands secrete an oily mixture known as sebum which consists of triglycerides, wax esters, fatty acids and the hydrocarbon squalene. Although they are absent from the palms and soles, they are prolific on the face and scalp, so it is very easy for sebum to be transferred to the fingers by touch. It is already known that the composition of sebum is affected by diet and gender, so would it be possible to use it to discriminate between male and female suspects?

Print collection

The team collected fingermarks from a total of 37 people aged 18-21, comprising 16 Caucasian males, 13 Caucasian females, 3 African American and 3 Asian males and 1 African American and 1 Asian female. Since this was a proof-of-principal study, the effects of various factors like diet, washing and the use of personal care products were discounted at this stage for later consideration.
The fingermarks were removed from the glass slides with wipes that were treated with a solvent mixture to remove the organic components. This extract was used for GC/MS analysis, with two added fatty acids as recovery standard and internal standard. The fatty acids present were resolved on a low polarity silarylene phase GC that is similar to 5% phenyl-95% dimethylpolysiloxane.
The fatty acids were identified by reference to a mixture of 37 fatty acid methyl esters and they were measured from the peak areas in the chromatograms. The amounts of each acid present could easily vary from person to person, so their measured ratios against hexadecanoic acid (HDA) were considered rather than their singular concentrations to give a degree of normalisation. This acid was chosen as a reference because it was prominent in every chromatogram.

Gender and race defined

Human sebum is known to secrete the so-called Delta6-fatty acids, which have a double bond in the 6-position, but (Z)-6-octadecenoic acid (ODA) was the only one detected. The absence of others might be due to their low concentrations in the fingermarks or possibly extraction losses or coelution from the GC column.
Other fatty acids were found and the ratios of a number of fatty acids were found to differ between race and gender. For instance, the ratios of ODA to HDA and of octadecenoic acid to HDA differentiated between Caucasian males and females, African American males and Asian males. An unidentified fatty acid which was tentatively identified as a C21-C22 isomer also differentiated between Caucasian males and females, Caucasian males and African American males, as well as Asian males.
Other ratios involving an unidentified C16-C17 fatty acid isomer made the same distinctions. The difficult identifications involved the African American females and Asian females. For some of the aforementioned acids, the ratios for these two groups fell within the range of other groups or the acids were not detected.
So, it might be possible to use fingermarks to gain more information on gender or race. This will provide support to data gleaned from the nuclear or mitochondrial DNA of fingermarks, which can be inconclusive due to low concentrations. However, the fatty acid data must be treated with caution at this stage. A far larger data set must be used along with a comprehensive statistical evaluation of the data. Factors like diet, cosmetic use and individual behaviour could also influence the results.