Palmitoylethanolamide, a non-psychotropic analgesic drugs “Magic bullet” or “multiple-target” strategies?

Summary

Two academic pharmacologists discussed this week the importance of the natural painkiller palmitoylethanolamide (PeaPure) for a variety of chronic pain states. Palmitoylethanolamide moved to the centre of the scientific attention since the Novel laureate professor Levi-Montalcini unravelled the mechanism of this wise molecule of the body.

The pharmacologists professor Di Marzo and Starowicz pointed out in the European Journal of Pharmacology (March) that palmitoylethanolamide is an analgesic natural compounds with multi-target mechanisms of action. This makes the molecule extremely interesting for the treatment of complex persistent somatic inflammatory pain, visceral inflammatory pain and neuropathic pain. Furthermore they discussed recent clinical trial data supporting the efficacy and safety of this endogenous, natural molecule.

Source: Katarzyna Starowicz, Vincenzo Di Marzo, Non-psychotropic analgesic drugs from the endocannabinoid system: “Magic bullet” or “multiple-target” strategies? European Journal of Pharmacology Available online 13 March 2013

Palmitoylethanolamide, an analgesic natural compounds with multi-target mechanisms of action

Katarzyna Starowicz and professor Vincenzo Di Marzo published this month their expert review, titel:

Non-psychotropic analgesic drugs from the endocannabinoid system: “Magic bullet” or “multiple-target” strategies?

The authors point out that the discovery of the endocannabinoid system and of endocannabinoid -degrading enzymes offers an important opportunity to develop new drugs against inflammatory and chronic pain potentially safer that CB1 or CB2 exogenous agonists, such as Cannabis (THC).

ALthough since this decade many pharmaceutical companies looked for enzyme inhibitors of endocannabinoids, the existence of multiple endocannabinoid -degradation pathways probably minimizes the impact of this pharmaceutical strategy to elevate endocannabinoid levels and activate CB receptors indirectly, because by inhibiting one enzyme alterative degradation pathway(s) may become activated.

Palmitoylethanolamide is highlighted by the authors as:

an analgesic natural compounds with multi-target mechanisms of action

PEA , they state “occurs in higher tissue concentrations than anandamide and produces its effects in a mostly cannabinoid receptor-independent manner. PEA is a naturally occurring C16:0 fatty acid derivative where the carboxylate function is amidated by the primary amine of ethanolamine.”

The authors point out that PEA has been shown to inhibit peripheral inflammation and mast cell degranulation, and exhibits a number of beneficial effects, including pain relief, as well as anti-allodynic and anti-hyperalgesic effects via multiple mechanisms, including TRPV1 activation/desensitization.

In general, PEA is thought to be involved in endogenous protective mechanisms that are activated in the body as a result of different types of tissue damage or stimulation of inflammatory responses and nociceptive fibers.

They discus the recent findings, supporting Levi-Montalcini’s findings from the 90s, that by modulating mast cell degranulation, PEA, in a concentration-dependent manner, reduces also NGF protein expression and release in the chronically inflamed tissues. Based on a great many experiments, the authors conclude:

The above data support an analgesic role played by PEA in persistent somatic inflammatory pain, visceral inflammatory pain and neuropathic pain

PEA is characterized as a natural multi-target compounds which has already been successful in the clinic.

Source: Katarzyna Starowicz, Vincenzo Di Marzo, Non-psychotropic analgesic drugs from the endocannabinoid system: “Magic bullet” or “multiple-target” strategies? European Journal of Pharmacology Available online 13 March 2013

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