Free radicals and the pathobiology of brain dopamine systems.

The lower limb flexion reflex in humans.

The variety of factors and events involved in neurodegeneration renders the subject a major challenge. Neurodegenerative disorders include a number of different pathological conditions, which share similar critical metabolic processes, such as protein aggregation and oxidative stress, both of which are associated with the involvement of metal ions. In this review, Alzheimer's disease, Parkinson's disease and prion disease are discussed, with the aim of identifying common trends underlying these devastating neurological conditions. Chelation therapy could be a valuable therapeutic approach, since metals are considered to be a pharmacological target for the rationale design of new therapeutic agents directed towards the treatment of neurodegeneration.

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The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy

Neurochemical modulation of sensory-motor reactivity: acoustic and tactile startle reflexes.

Among the biopolymers, melanins are unique in many respects. The other essential biopolymers - proteins, nucleic acids, and carbohydrates - are chemically well characterized; their precursors (monomer units) and modes of connection between the monomer units are known, and sequences of their connection can be determined with well-established methodologies. In contrast, we still do not have a method to determine accurately the ratio of various units present in melanins. This is largely because of the chemical properties of melanins, such as their insolubility over a broad range of pH, the heterogeneity in their structural features, and also because of the lack of methods that can split melanin polymers into their monomer units (all other biopolymers can be hydrolysed to the corresponding monomer units). To overcome this difficulty, we developed a rapid and sensitive method for quantitatively analysing eumelanin and pheomelanin in biological samples by chemical degradation methods followed by HPLC determination. This HPLC microanalytical method for characterizing eumelanin and pheomelanin has become a useful tool for the study of melanogenesis. This review will summarize the usefulness and limitations of the various chemical and spectrophotometric methods used to analyse melanins at the biochemical, cellular, and tissue levels. Emphasis is given on the usefulness of 4-amino-3-hydroxyphenylalanine as a specific marker of pheomelanin.

https://onlinelibrary.wiley.com/doi/pdf/10.1034/j.1600-0749.2002.02017.x

Advanced chemical methods in melanin determination.

We examined the effect of trazodone (TR), a non-tricyclic antidepressant drug with an unknown mechanism of action, as well as its supposed metabolitesβ-(3-oxo-s-triazolo-[4, 3 a]-pyridin-2-yl-propionic acid (OTPA) and 1-(m-chlorophenyl)-piperazine (CPP) on the serotonin (5-HT) system in a model of the hind limb flexor reflex of the spinal rat.

Trazodone, a central serotonin antagonist and agonist.

The effects of serotonergic and antiserotonergic drugs on the hind limb flexor reflex (measured as a contraction of musculus tibialis anterior or as a flexion of the paw) in the spinal rat was studied. All serotonergic drugs used (L-5-hydroxytryptophan, L-tryptophan, LSD, fenfluramine, p-chloroamphetamine) stimulate the flexor reflex. Serotonin receptor blockers (cyproheptadine, WA-335, methergoline), which given alone are inactive, inhibit the stimulation induced by serotonergic drugs but do not influence that one caused by noradrenergic agents (amphetamine, clonidine). Both types of stimulation (serotonergic and noradrenergic) are antagonized by noradrenaline receptor blockers (phenoxybenzamine, clozapine). The antiserotonergic action of serotonin antagonists used was confirmed on the basis of the antagonism to the head twitches induced by L-5-hydroxytryptophan. The flexor reflex in the spinal rat may be a good model to evaluate the effect on the central (spinal cord) serotonin receptor and to differantiat this effect from that on the noradrenaline system.

The effects of serotonergic and antiserotonergic drugs on the flexor reflex of spinal rat: a proposed model to evaluate the action on the central serotonin receptor.

It was found that spiperone and pimozide in doses which themselves do not influence the flexor reflex of the hind limb of the spinal rat inhibit stimulation of this reflex induced by serotoninomimetic drugs (LSD and fenfluramine). Higher doses of spiperone depress the flexor reflex and inhibit the stimulating effect of clonidine. Pimozide has no such effect. Haloperidol in doses which do not influence the action of LSD and fenfluramine produces a depression of the flexor reflex and antagonizes the action of clonidine. Our findings indicate that, irrespective of their antidopamine action, spiperone has a central antiserotonin effect and an antinoradrenaline one, pimozide—an antiserotonin one and haloperidol—an antinoradrenaline one.

The effect of haloperidol, spiperone and pimozide on the flexor reflex of the hind limb of the spinal rat.

ANDBN, N.-E., GRABOWSKA, M. & STROMBOM, U. (1976). Naunyn Schmiedebergs Arch. Pharmac., 292, 43-52. ANTON, A. H. & SAYRE, D. F. (1962). J. Pharmac. exp. Ther., 138, 360-375. BRODIE, B. B., COSTA, E., DLABAC, A., NEFF, N. H. & SMOOKLER, H. H. (1966). Ibid., 154, 493-498. DE JONG, W. (1974). Eur. J. Pharmac., 29, 179-181. FINCH, L. & LEACH, G. D. H. (1970). Br. J. Pharmac., 39, 317-324. GAGNON, D. J. & MELVILLE, K. I. (1968). Can. J. Physiol. Pharmac., 46, 595-599. GLOWINSKI, J. & IVERSEN, L. L. (1966). J. Neurochem., 13, 655-669.

W. Palider

Papers

Trazodone, a central serotonin antagonist and agonist.

The effects of serotonergic and antiserotonergic drugs on the flexor reflex of spinal rat: a proposed model to evaluate the action on the central serotonin receptor.

The effect of haloperidol, spiperone and pimozide on the flexor reflex of the hind limb of the spinal rat.

The influence of mescaline on the flexor reflex of the hind limb of the spinal rat.

2040 – SEROTONINMIMETIC PROPERTIES OF 1-/m-CHLORPHENYL-/-PIPERAZINE, A POTENTIAL TRAZODONE METABOLITE