Endocannabinoid reuptake inhibitors (eCBRIs), also called cannabinoid reuptake inhibitors (CBRIs), are

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...

s which limit the reabsorption of

endocannabinoid Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

by the releasing neuron.

Pharmacology

The method of transport of endocannabinoids through the cell membrane and cytoplasm to their respective degradation enzymes has been rigorously debated for nearly two decades, and a putative endocannabinoid membrane transporter was proposed. However, as lipophilic molecules endocannabinoids readily pass through the cell lipid bilayer without assistance and would more likely need a chaperone through the cytoplasm to the endoplasmic reticulum where the enzyme FAAH is located. More recently

fatty acid-binding proteins In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...

(FABPs) and

heat shock protein Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including exp ...

s (

Hsp70 The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an importa ...

s) have been described and verified as such chaperones, and their inhibitors have been synthesized. The inhibition of endocannabinoid reuptake raises the amount of those neurotransmitters available in the

synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

and therefore increases

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...

. Following the increase of neurotransmission in the endocannabinoid system is the stimulation of its functions which, in humans, include: suppression of

pain perception Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, co ...

(analgesia), increased

appetite Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to reg ...

mood Mood may refer to: *Mood (psychology), a relatively long lasting emotional state Music *The Mood, a British pop band from 1981 to 1984 * Mood (band), hip hop artists * ''Mood'' (Jacquees album), 2016 * ''Moods'' (Barbara Mandrell album), 1978 ...

elevation and inhibition of short-term

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered ...

Examples of eCBRIs

* AM404 - an active metabolite of

Paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferi ...

. * AM1172 * LY-2183240 * O-2093 * OMDM-2 * UCM-707 *

VDM-11 VDM-11 is a potent cannabinoid reuptake inhibitor. It is light-sensitive and must be stored within an inert gas such as argon Argon is a chemical element with the symbol Ar and atomic number 18. It is in group 18 of the periodic table and ...

* Guineensine * WOBE437 and RX-055Nicolussi S, Chicca A, Soeberdt M, Abels C, Viveros.Paredes JM, Aparisi-Rey A, Lutz B, Gertsch J. WOBE437 - Prototype of a novel class of potent, selective endocannabinoid reuptake inhibitors. BPS 6th Eur Workshop on Cannabinoid Research 2013.

References

{{Cannabinoidergics Neurochemistry Cannabinoids Endocannabinoid reuptake inhibitors

Pharmacology

Examples of eCBRIs

See also

References