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Anti-Parkinson & alpha2

Key message: compounds combining D2/D3 partial agonism and alpha2 adrenoceptor antagonism may exhibit improved anti-Parkinson therapeutic properties. 

  • Extensive in vitro affinity and signalling analysis at 20 different receptors shows that antiparkinsonian agents differ widely in their mechanisms of action.
  • Alpha2 adrenoceptor antagonism is known to exert prolocomotor activity in animal models of Parkinson's disease.
  • Current antiparkinsonian agents exhibit diverse agonist or antagonist properties at alpha2 receptors. 
  • The antiparkinsonian agent, piribedil (Trivastal ®) exhibits alpha2 adrenoceptor antagonism, in addition to D2 & D3 receptor partial agonism.
# Article Title
1 Anatomically Selective Serotonergic Type 1A and Serotonergic Type 2A Therapies for Parkinson's Disease: An Approach to Reducing Dyskinesia without Exacerbating Parkinsonism? REVIEW
2 [35S]-GTPgammaS autoradiography reveals alpha2 adrenoceptor-mediated G-protein activation in amygdala and lateral septum.
3 Antiparkinsonian agent piribedil displays antagonist properties at native, rat, and cloned, human alpha2-adrenoceptors: cellular and functional characterization. PDF
4 Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. PDF
5 Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D2-like receptor and alpha1/alpha2-adrenoceptor. PDF
6 Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT1 and 5-HT2, receptor subtypes. PDF
7 Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra.
8 Actions of alpha2 adrenoceptor ligands at alpha2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for alpha2A adrenoceptors.
9 Ligand modulation of [35S]GTPgammaS binding at human alpha2A, alpha2B and alpha2C adrenoceptors.
10 Anticataleptic properties of alpha2 adrenergic antagonists in the crossed leg position and bar tests: differential mediation by 5-HT1A receptor activation.
11 S18616, a highly potent, spiroimidazoline agonist at alpha(2)-adrenoceptors: I. Receptor profile, antinociceptive and hypothermic actions in comparison with dexmedetomidine and clonidine.
12 Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha2-adrenergic receptors, serotonin 5-HT1A, 5-HT1B, 5-HT1D and dopamine D2 and D3 receptors. Significance for the modulation of frontocortical monoaminergic transmission.
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