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.