Guineesine (or guineensine) is a compound isolated from

long pepper Long pepper (''Piper longum''), sometimes called Indian long pepper or ''pippali'', is a flowering vine in the family Piperaceae, cultivated for its fruit, which is usually dried and used as a spice and seasoning. Long pepper has a taste sim ...

(''Piper longum'') and

black pepper Black pepper (''Piper nigrum'') is a flowering vine in the family Piperaceae, cultivated for its fruit (the peppercorn), which is usually dried and used as a spice and seasoning. The fruit is a drupe (stonefruit) which is about in diameter ...

(''Piper nigrum''). It was first isolated, studied and named from '' Piper guineense''.

Research

Guineensine inhibits the cellular reuptake of

anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

and

2-arachidonoylglycerol 2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is pres ...

in a mouse model ( EC₅₀ = 290 nM). This causes an increase in the activity of the two

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

s which are classified as

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

cannabinoids Cannabinoids () are several structural classes of compounds found primarily in the ''Cannabis'' plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoa ...

. Guineesine can dose-dependently produce cannabimimetic effects in a mouse model which are indicated by potent

catatonic Catatonia is a complex syndrome most commonly seen in people with underlying mood disorders, such as major depressive disorder, or psychotic disorders, such as schizophrenia. People with catatonia exhibit abnormal movement and behaviors, wh ...

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

, hypo-locomotive and hypo-thermic effects. In addition, the analgesic and catatonic effects were reversed by the

cannabinoid receptor type 1 Cannabinoid receptor 1 (CB1), is a G protein-coupled cannabinoid receptor that in humans is encoded by the ''CNR1'' gene. And discovered, by determination and characterization in 1988, and cloned in 1990 for the first time. The human CB1 rece ...

(CB1)

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

rimonabant Rimonabant (also known as SR141716; trade names Acomplia, Zimulti) is an anorectic antiobesity drug approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects; it was never approved in the United State ...

. Guineesine is also a

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

(MAOI) ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' ( IC₅₀ = 139.2 μM).

References

{{Reflist, 30em Alkaloids found in plants Benzodioxoles Carboxamides Monoamine oxidase inhibitors Cannabinoids Endocannabinoid reuptake inhibitors