BACKGROUND AND OBJECTIVE: Tricyclic antidepressants are commonly employed orally to treat major depressive disorders and have been shown to be of substantial benefit in various chronic pain conditions. Among other properties they are potent Na+ channel blockers in vitro and show local anaesthetic properties in vivo. The present study aimed to determine their differential neurotoxicity, and that of novel derivatives as prerequisite for their potential use in regional anaesthesia. METHODS: To directly test neurotoxicity in adult peripheral neurons, the culture model of dissociated adult rat primary sensory neurons was employed. Neurons were incubated for 24 h with amitriptyline, N-methyl-amitriptyline, doxepin, N-methyl-doxepin, N-propyl-doxepin, desipramine, imipramine and trimipramine at 100 mumol, and at concentrations correlating to their respective potency in blocking sodium channels. RESULTS: All investigated substances showed considerable neurotoxic potency as represented in significantly decreased neuron numbers in cultures as compared to controls. Specifically, doxepin was more neurotoxic than amitriptyline, and both imipramine and trimipramine were more toxic than desipramine or amitriptyline. Novel derivatives of tricyclic antidepressants were, in general, more toxic than the parent compound. CONCLUSIONS: Tricyclic antidepressants and novel derivatives thereof show differential neurotoxic potential in vitro. The rank order of toxicity relative to sodium channel blocking potency was desipramine < amitriptyline < N-methyl amitriptyline < doxepin < trimipramine < imipramine < N-methyl doxepin < N-propyl doxepin.
BACKGROUND AND OBJECTIVE: Tricyclic antidepressants are commonly employed orally to treat major depressive disorders and have been shown to be of substantial benefit in various chronic pain conditions. Among other properties they are potent Na+ channel blockers in vitro and show local anaesthetic properties in vivo. The present study aimed to determine their differential neurotoxicity, and that of novel derivatives as prerequisite for their potential use in regional anaesthesia. METHODS: To directly test neurotoxicity in adult peripheral neurons, the culture model of dissociated adult rat primary sensory neurons was employed. Neurons were incubated for 24 h with amitriptyline, N-methyl-amitriptyline, doxepin, N-methyl-doxepin, N-propyl-doxepin, desipramine, imipramine and trimipramine at 100 mumol, and at concentrations correlating to their respective potency in blocking sodium channels. RESULTS: All investigated substances showed considerable neurotoxic potency as represented in significantly decreased neuron numbers in cultures as compared to controls. Specifically, doxepin was more neurotoxic than amitriptyline, and both imipramine and trimipramine were more toxic than desipramine or amitriptyline. Novel derivatives of tricyclic antidepressants were, in general, more toxic than the parent compound. CONCLUSIONS: Tricyclic antidepressants and novel derivatives thereof show differential neurotoxic potential in vitro. The rank order of toxicity relative to sodium channel blocking potency was desipramine < amitriptyline < N-methyl amitriptyline < doxepin < trimipramine < imipramine < N-methyl doxepin < N-propyl doxepin.
Authors: Philipp Lirk; Magdalena Flatz; Ingrid Haller; Barbara Hausott; Stephan Blumenthal; Markus F Stevens; Suzuko Suzuki; Lars Klimaschewski; Peter Gerner Journal: Reg Anesth Pain Med Date: 2012 Nov-Dec Impact factor: 6.288
Authors: Hila Epstein-Barash; Iris Shichor; Albert H Kwon; Sherwood Hall; Michael W Lawlor; Robert Langer; Daniel S Kohane Journal: Proc Natl Acad Sci U S A Date: 2009-04-13 Impact factor: 11.205
Authors: Lara Bieler; Michael Vogl; Michael Kirchinger; Corinna Urmann; Herbert Riepl; Christine Bandtlow; Lars Klimaschewski; Ludwig Aigner; Sebastien Couillard-Despres Journal: Front Cell Neurosci Date: 2019-07-24 Impact factor: 5.505