Anxiety peptides

Guidotti and Ferrero95 isolated from human and rat brain extracts neuroactive peptides that interact with the receptors at which benzodiazepines (e.g. Valium and Librium) induce biological effects. The DBI peptide 48 ( anxiety peptide ), an endogenous ligand of the benzodiazepine receptor, causes anxiety, in contrast to the benzodiazepines. 

Marx, J.L. 1985. Anxiety peptide foundin brain Science 227 934. 

Anxiety peptide, diazepam-binding inhibitor peptide. 

A newer, highly experimental approach to anxiety therapy is the use of antisense oligonucleotides to the anxiogenic peptide, NPY (44). 

Finally, the peptide can induce anxiety and panic in normal and anxious volunteers. Some synthetic CCK-B receptor antagonists are chemically similar to the benzodiazepine anxiolytics. Again, the clinical role of CCK manipulation in anxiety remains to be resolved. 

Nakajima, M, Unui, A, Asakawa, A, Momose, K, Ueno, N, Teranishi, A, Baba, S and Kasuga, M (1998) Neuropeptide Y produces anxiety via Y2-t5 pe receptors. Peptides 19 359-363. 

The neuropeptide Y (NPY) belongs to a family of peptides that includes peptide YY and pancreatic polypeptide, and it is associated with several diseases such as asthma, immune system disorders, inflammatory diseases, anxiety, depression and diabetes mellitus. NPY is found in the central and peripheral nervous system, and its biological functions are mediated by interactions with five receptor sub-types, i.e. Yl, Y2, Y4, Y5 and Y6. Several studies indicate that the feeding behavior is influenced by interactions between NPY and Yl and Y5. Deswal and Roy used Cerius descriptors and genetic function approximation QSAR to investigate the structural determinants for the inhibition potency of 24 compounds with the general structure 4 for the NPY Y5 receptor [31]. The best QSAR (H = 0.720,... 

Neuropeptide S (NPS) is a recently discovered bioactive peptide that has emerged as a new signaling molecule in the complex circuitry that modulates sleep-wakefulness and anxiety-like behavior. The peptide precursor is expressed most prominently in a novel nucleus located in the perilocus coeruleus, a brain structure with well-defined functions in arousal, stress, and anxiety. NPS was also found to induce anxiolytic-like behavior in a battery of four different tests of innate responses to stress. Infusion of NPS potently increases wakefulness and suppresses non-REM (NREM) and REM sleep (Xu et al, 2004). NPS binds to a G-protein-coupled receptor, the NPS receptor, with nanomolar affinity activation of the receptor mobilizes intracellular calcium. The NPS receptor is expressed throughout the brain, particularly in regions relevant to the modulation of sleep and waking, in the tuberomammillary region, lateral hypothalamus, and medial thalamic nuclei. 

To test the potential involvement of SP in the modulation of anxiety, some studies used a systemic administration of this peptide. The results were, however. 

Neuropeptide Y (NPY) is a highly conserved 36 amino acid peptide of the pancreatic polypeptide family that is widely distributed throughout the mammalian brain. Y1 and Y2 receptors represent the major subtypes expressed in brain areas known to be activated upon anxiogenic stimulation, thus providing the rationale for studying the involvement of NPY and its receptor subtypes in anxiety-related behaviour (Kask et al. 2002). Other receptor subtypes in... 

Walther et al. 1999). Increased levels of anxiety after central administration of the glucagon-like peptide-1 (7-36) amide have been reported by Kinzig et al. (2003). 

Wiedemann K, Jahn H, Kellner M (2000) Effects of natriuretic peptides upon hypothalamo-pituitary-adrenocortical system activity and anxiety behaviour. Exp Clin Endocrinol Diabetes 108 5-13... 

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