Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Sunday, November 20, 2011

A Review of the Opioid Receptor System

MOR - Micro Receptor (OP3)

Locations: brainstem (medulla, LC), medial thalamus, lymbic circuitry (NA, VTA, amygdala), PAG, anterior cingulate, cerebral cortex, dorsal spinal cord & SG, and GI tract

Ligands: endomorphin, enkephalin, DAMGO)

u1 - analgesia in the brain (supraspinal analgesia), euphoria, excitement, mesolimbic reward, psycho-dependence

u2 - analgesia in the spine (spinal analgesia), sedation, anxiolysis, respiratory depression, constipation, itching, physical dependence, tolerance

u3 - unknown function

2 subtypes of the mu receptor (MOR) have been characterized. Mu-1 receptors affect emotional state and emotional response (functions of mood), wherease mu-2 receptors affect arousal, physical dependence, and respiration (autonomic functions). Both subtypes mediate analgesia (pain relief), though perhaps through different locations (brain vs spinal cord). We can assume that mu-1 receptors are predominantly active in forebrain structures such as the limbic areas, while mu-2 receptors primarily affect activity in lower structures such as the hypothalamus, brainstem, and spinal cord, which modulate function at a more basal level.

The presence of two MOR subtypes was deducted from research which dissociated supraspinal morphine analgesia from respiratory depression and constipation, through selective application of the mu antagonist naloxonazine.

A 3rd subtype of mu receptor has been theorized based on the analgesia produced by morphine 6-substituted analogues in mu1 and 2 knockout subjects. This third subtype interacts with opioid alkaloid compounds and not opioid peptides, and has been referred to as the morphine-6-glucuronide receptor; only certain compounds are believed to interact with this subtype - specifically, morphine analogues with C-6 substitutions such as morphine-6-glucuronide, 6-acetylmorphine, heterocodeine, and possibly fentanyl.

KOR - Kappa Receptor (OP2)

Locations: brainstem, hypothalamus, dorsal spinal cord & SG, PAG, claustrum, limbic circuitry

Ligands: dynorphin, enadoline, ketocyclazocine

Associated with spinal analgesia, dysphoria, aversion, miosis, sedation, diuresis (increased urination), psychotomimesis, anti-itching, counteraction of mu-agonist effects, anti-addictive effect, dopamine inhibition, mu & dopamine receptor upregulation

At least 2 subtypes of kappa receptor have been characterized. Kappa is the endogenous dynorphin receptor. KOR is involved in spinal analgesia, and counteraction to many mu-mediated effects (namely euphoria and addiction).

DOR - Delta Receptor (OP1)

Locations: neocortex, caudate nucleus, putamen, amygdala, olfactory bulbs, pons, dorsal spinal cord & SG

Ligands: enkephalin, deltorphin, DPDPE

Involved in anxiolysis, antidepressant properties, respiratory stimulation or depression, upregulation of brain-derived neurotrophic hormone, cardioprotection, potentiation of mu analgesia

2 subtypes of delta receptor have been characterized. Its role is not well established, but delta receptors are believed to be involved in potentiating mu-receptor analgesia, dependence, and reward.

ORL1 - Orphan Receptor, Opioid-Like-Receptor 1 (OP4)

(Ligand: nociceptin)

hyperalgesia (pain), anxiety, counteraction of mu-agonist effects, anorexia or hunger
Endogenous receptor for nociceptin, the neurotransmitter implicated in transduction of pain signals.

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