Melatonin and Its Agonists in Pain Modulation and Its Clinical Application.

Melatonin and its agonists in pain modulation and its clinical application.

Arch Ital Biol. 2012 Dec; 150(4): 274-92
Srinivasan V, Zakaria R, Jeet Singh H, Acuna-Castroviejo D

Melatonin, the hormone of darkness has many physiological functions in the body and also exerts a number of pharmacological effects. Most of these actions of melatonin are mediated through melatonin membrane receptors like MT1/MT2 receptors or through nuclear orphan receptors like RZR/ROR receptors or through calcium binding proteins in the cytosol. The finding that pain perception is circadian in nature has prompted many to suggest that “pain modulation” is one of the most important physiological functions of melatonin. By using a number of animal models of pain perception, it has been found that melatonin exerts antinociceptive and antiallodynic effects. Number of studies has shown that melatonin modulates pain perception by acting through opioid receptors, NMDA receptors and G-protein, and they have been analyzed using specific antagonists like naloxone or NMDA-G protein receptor antagonists. Recently it has been shown that melatonin exerts its antinociceptive effects through MT1 and MT2 melatonergic receptors located in the dorsal region of the spinal cord as well as in various parts of the brain concerned with pain modulation. Evidences for this have been obtained by using common melatonergic receptor antagonist like luzindole or specific MT2 receptor antagonist like 4P-PDOT or K-185. In a few clinical studies undertaken during surgery, melatonin has been shown to have analgesic effects. Melatonin is emerging as a new analgesic drug with a novel mechanism of actions and has the potential to be used as a natural pain killer in inflammatory, neuropathic pain conditions and also during surgical procedures. HubMed – drug


The 5-hydroxytryptamine (serotonin) receptor 6 agonist EMD 386088 ameliorates ketamine-induced deficits in attentional set shifting and novel object recognition, but not in the prepulse inhibition in rats.

J Psychopharmacol. 2013 Mar 11;
Nikiforuk A, Fijal K, Potasiewicz A, Popik P, Kos T

Preclinical data suggest that the 5-hydroxytryptamine (serotonin) 6 (5-HT6) receptor may be a potential target for the development of new therapies for treating cognitive dysfunctions in schizophrenia and other central nervous system disorders. Recent evidence indicates that not only blockade but also activation of 5-HT6 receptors exerts procognitive effects. Nevertheless, little is known about the potential efficacy of 5-HT6 receptor agonists in models of schizophrenia-like cognitive deficits.The aim of the present study was to evaluate the effects of the 5-HT6 receptor agonist, EMD 386088, on the ketamine-induced deficits in the attentional set-shifting task (ASST), novel object recognition (NOR) task and prepulse inhibition (PPI) task in rats.Acute administration of EMD 386088 (2.5 and 5 mg/kg, intraperitoneally) to Sprague-Dawley rats reversed the deficit in the ASST induced by repeated ketamine administration. Moreover, the ketamine-induced deficit in the NOR task was ameliorated by EMD 386088 at a dose of 5 mg/kg. However, in contrast to the antipsychotic drug clozapine, the 5-HT6 agonist did not affect PPI disrupted by ketamine.The present study demonstrated the beneficial effects of the 5-HT6 agonist in ameliorating some of the ketamine-induced deficits relevant to schizophrenia. It thus seems likely that the 5-HT6 receptor activation may represent a useful pharmacological approach to the treatment of cognitive disturbances observed in this disorder. HubMed – drug


Solubilization of poorly soluble photosensitizer hypericin by polymeric micelles and polyethylene glycol.

Gen Physiol Biophys. 2013 Mar 11;
Búzová D, Kasák P, Miškovský P, Jancura D

Hypericin (Hyp) is a promising photosensitizer for photodiagnostic and photodynamic therapy of cancer. However, Hyp has a large conjugated system and in aqueous solutions forms insoluble aggregates which do not possess biological activity. This makes intravenous injection of Hyp problematic and restricts its medical applications. To overcome this problem, Hyp is incorporated into drug delivery systems which can increase its solubility and bioavailability. One of the possibilities is utilization of polymeric micelles. The most used hydrophilic block for preparation of polymeric micelles is polyethylen glycol (PEG). PEG is a polymer which for its lack of immunogenicity, antigenicity and toxicity obtained approval for use in human medicine. In this work we have studied the solubilization of Hyp aggregates in the presence of PEG-PE and PEG-cholesterol micelles. The concentration of polymeric micelles which allows total monomerization of Hyp corresponds to the critical micellar concentration of these micelles (~10-6 M). We have also investigated the effect of the molecular weight and concentration of PEG on the transition of aggregated Hyp to its monomeric form. PEGs with low molecular weight (< 1000 g/mol) do not significantly contribute to the solubilization of Hyp. However, PEGs with molecular weight > 2000 g/mol efficiently transform Hyp aggregates to the monomeric state of this photosensitizer. HubMed – drug