Related Experiment Video
Updated: May 6, 2026

Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
Published on: August 10, 2012
Synthesis and neuromodulatory effects of TRH-related peptides: inhibitory activity on catecholamine release in vitro
Luigi Brunetti1, Annalisa Chiavaroli, Alessandra Cocco
1Department of Pharmacy, G. d'Annunzio University, via dei Vestini 31, 66013 Chieti, Italy. mvacca@unich.it.
Background:
A detailed comprehension of central mechanisms underlying feeding behavior holds considerable promise for the treatment of alimentary disorders.
Methods:
In order to elucidate the tight interrelationships occurring at the hypothalamic neuronal endings between aminergic neurotransmitters and co-localized appetite modulators, we initially studied the effects of two anorexigenic peptides structurally related to thyrotropin-releasing hormone (TRH, 1), namely cyclo(His-Pro) (CHP, 2) and pGlu-His-Gly-OH (3), on [(3)H]-norepinephrine and [(3)H]-dopamine release from perfused rat hypothalamic synaptosomes. Furthermore, a number of TRH and CHP analogues were synthesized and tested for their ability to influence neurotransmitter release in the selected neuronal model.
Results:
Peptide 3 showed only a slight inhibitory activity on norepinephrine release, whereas no effect was observed for compound 2. TRH analogue 8, metabolically stabilized by the replacement of pyroglutamate with the pyrohomocysteic acid (pHcs), was found to be inactive. Conversely, a significant inhibitory effect on dopamine and norepinephrine release was observed for the CHP-related diketopiperazines cyclo(Leu-Pro) (11) and cyclo(His-Gly) (14).
Conclusions:
These results suggest a potential role for cyclo-dipeptides 11 and 14 in the hypothalamic modulation of appetite suppressant circuitry.
Related Concept Videos
Drugs Affecting Neurotransmitter Synthesis
Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
Drugs Affecting Neurotransmitter Release or Uptake
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
Adrenergic Neurons: Neurotransmission
Synthesis: Catecholamine synthesis requires tyrosine, which...
Neurochemical Transmission: Sites of Drug Action

