KM-416, a novel phenoxyalkylaminoalkanol derivative with anticonvulsant properties exerts analgesic, local anesthetic, and antidepressant-like activities. Pharmacodynamic, pharmacokinetic, and forced degradation studies

Antinociceptive and Antiallodynic Activity of Some 3-(3-Methylthiophen-2-yl)pyrrolidine-2,5-dione Derivatives in Mouse Models of Tonic and Neuropathic Pain

“…The results reported herein are a continuation of our research in the group of 3-(3-methylthiophen-2-yl)pyrrolidine-2,5-dione derivatives, with previously confirmed anticonvulsant and analgesic activity [ 18 ]. Similar studies for chemically diversified substances were previously reported by our team [ 21 , 22 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ].…”

“…Relevant sites of action include voltage-gated ion channels (sodium and calcium), ligand-gated ion channels transient receptor TRPV1, and others [ 46 ]. Furthermore, ASDs that block sodium channels, and high-frequency action potential firing, are effective in the treatment of neuropathic pain and seizures [ 28 , 32 , 47 ]. Taking this into account, three compounds 3 , 6 , and 9, for which affinity for calcium, sodium, and TRPV1 channels had been previously confirmed [ 18 ], were examined to establish their antiallodynic efficacy in the oxaliplatin-induced neuropathic pain model.…”

Design, Synthesis and Anticonvulsant Activity of New Phenoxyalkyl, Phenoxyethoxyethyl and Phenoxyacetyl Derivatives of Aminoalkanols

“…The design of new compounds was based on structure-activity relationship analysis for previously synthesized and tested compounds. [10][11][12][13][14][15][16][17][18][19][20][21] All designed structures were analogues or homologs of reference compounds I-VI (Figure 1) and are presented in Table 1. There were three sites of structural modifications: (1) substitution of aromatic ring, (2) linker and (3) aminoalkanol moiety.…”

“…The majority of designed compounds were derivatives of ethanolamine, which was dictated by the structural similarity to antiarrhythmic drugs and our previous experience (Figure 1). [10][11][12][13][14][15][16][17][18][19][20][21] However, in case of several compounds the distance between the oxygen and nitrogen atoms was prolonged in order to study the impact of this structural modification on pharmacological profile of the compound. In case of chiral aminoalkanols, in most cases we synthesized racemic mixtures first and in case of their activity -also the enantiomers.…”

“…Previous studies conducted by our group brought interest to a group of phenoxyalkyl, phenoxyethoxyethyl and phenoxyacetyl derivatives of aminoalkanols. [10][11][12][13][14][15][16][17][18][19][20][21] The research resulted in the development of centrally active compounds (selected of which are presented in Figure 1), related in chemical structure to neurotransmitters (such as noradrenaline) and antiarrhythmic drugs with proven anticonvulsant activity (e. g. propranolol and mexiletine). The compounds were characterized by anticonvulsant activity in vivo, while some of them showed also analgesic activity in neuropathic pain.…”