59182-38-6Relevant academic research and scientific papers
Anti-allodynic effect of 2-(aminomethyl)adamantane-1-carboxylic acid in a rat model of neuropathic pain: A mechanism dependent on CaV2.2 channel inhibition
Zoidis, Grigoris,Sandoval, Alejandro,Pineda-Farias, Jorge Baruch,Granados-Soto, Vinicio,Felix, Ricardo
, p. 1797 - 1803 (2014)
Neuropathic pain is a serious physical disabling condition resulting from lesion or dysfunction of the peripheral sensory nervous system. Despite the fact that the mechanisms underlying neuropathic pain are poorly understood, the involvement of voltage-gated calcium (CaV) channels in its pathophysiology has justified the use of drugs that bind the CaV channel α2δ auxiliary subunit, such as gabapentin (GBP), to attain analgesic and anti-allodynic effects in models involving neuronal sensitization and nerve injury. GBP binding to α2δ inhibits nerve injury-induced trafficking of the α1 pore forming subunits of CaV channels, particularly of the N-type, from the cytoplasm to the plasma membrane of pre-synaptic terminals in dorsal root ganglion neurons and dorsal horn spinal neurons. In the search for alternative forms of treatment, in this study we describe the synthesis and pharmacological profile of a GABA derivative, 2-aminoadamantane-1-carboxylic acid (GZ4), which displays a close structure-activity relationship with GBP. Behavioral assessment using von Frey filament stimuli showed that GZ4 treatment reverted mechanical allodynia/hyperalgesia in an animal model of spinal nerve ligation-induced neuropathic pain. In addition, using the patch clamp technique we show that GZ4 treatment significantly decreased whole-cell currents through N-type Ca V channels heterologously expressed in HEK-293 cells. Interestingly, the behavioral and electrophysiological time course of GZ4 actions reflects that its mechanism of action is similar but not identical to that of GBP. While GBP actions require at least 24 h and imply uptake of the drug, which suggests that the drug acts mainly intracellularly affecting channels trafficking to the plasma membrane, the faster time course (1-3 h) of GZ4 effects suggests also a direct inhibition of Ca2+ currents acting on cell surface channels.
Synthesis of 1,2-annulated adamantane heterocycles: structural determination studies of a bioactive cyclic sulfite
Zoidis, Grigoris,Benaki, Dimitra,Myrianthopoulos, Vassilios,Naesens, Lieve,Clercq, Erik De,Mikros, Emmanuel,Kolocouris, Nicolas
, p. 2671 - 2675 (2009)
The novel heterocycle 3-oxatetracyclo[5.3.1.15,9.02,5]dodecane 4 is prepared by a simple and effective method, involving synthesis of the corresponding 2-hydroxy-1-adamantanomethanol followed by its intramolecular cyclization with th
Halogenated amino methyl adamantane derivatives
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, (2008/06/13)
Novel 2-substituted-1-methylamino adamantanes of formula: STR1 where X is hydroxyl or halogeno, and R1, R2 and R3 are hydrogen or C1-4 alkyl or R2 and R3 together with the nitrogen form a heterocyclic ring, having anti-Parkinsonian activity, pharmaceutical formulations containing the active adamantanes and novel 4-protoadamantane spiro oxirane and 1,2-difunctionalized intermediates useful in the preparation of the final products of the invention.
