D-neuron, ligand neuron of trace amine-associated receptor 1 (TAAR1): Key of novel non-D2 receptor-binding antipsychotics
Department of Psychiatry, Iwaki City Medical Center, Iwaki, Japan.
Research Article
International Journal of Biology and Pharmacy Research Archive, 2021, 01(01), 031–038.
Article DOI: 10.53771/ijbpra.2021.1.1.0027
Publication history:
Received on 19 September 2021; revised on 16 October 2021; accepted on 18 October 2021
Abstract:
The latest psychopharmacological study showed effectiveness of a novel non-D2-receptor-binding drug, SEP-363856, for the treatment of schizophrenia. The compound is trace amine-associated receptor 1 (TAAR1) full agonist and also 5-hydroxytryptamin 1A (5-HT 1A) receptor partial agonist. I found the TAAR1 ligand neuron, D-neuron, in the striatum and nucleus accumbens (Acc), a neuroleptic acting site, of human brains, though failed to find in the homologous area of monkey brains. To study human D-neuron functions, total of 154 post-mortem brains, and a modified immunohistochemical method using high qualified antibodies against monoamine-related substances, was applied. The number of D-neuron in the caudate nucleus, putamen, and Acc was reduced in post-mortem brains with schizophrenia. The reduction was significant (p<0.05) in Acc. I proposed “D-cell hypothesis of schizophrenia”, that NSC dysfunction-based D-neuron reduction is cellular and molecular basis of mesolimbic dopamine (DA) hyperactivity, progressive pathophysiology and prospectiveness of TAAR1 medicinal chemistry, emphasizing importance of D-neuron.
Keywords:
TAAR1; Dopamine; D-neuron: Schizophrenia; medicinal chemistry; SEP-3F3F5F
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