Orexin A (hypocretin-1) levels are not reduced while cocaine/amphetamine regulated transcript levels are increased in the cerebrospinal fluid of patients with multiple sclerosis: no correlation with fatigue and sleepiness.

Background: Fatigue and sleep disturbance are common features of multiple sclerosis (MS). Our objectives were to determine cerebrospinal fluid levels of orexin A (hypocretin-1), a hypothalamic peptide involved in sleep, in patients with MS, and correlate them with fatigue, sleepiness, and levels of cocaine and amphetamine regulated transcript (CART) another neuropeptide regulating metabolism with wider nervous system distribution.

Methods: Consecutive patients with MS (n=34), other inflammatory (n=24) or non-inflammatory (n=42) neurological diseases, undergoing lumbar puncture were investigated.

Discovery of a dual action first-in-class peptide that mimics and enhances CNS-mediated actions of thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) displays multiple CNS-mediated actions that have long been recognized to have therapeutic potential in treating a wide range of neurological disorders. Investigations of CNS functions and clinical use of TRH are hindered, however, due to its rapid degradation by TRH-degrading ectoenzyme (TRH-DE). We now report the discovery of a set of first-in-class compounds that display unique ability to both potently inhibit TRH-DE and bind to central TRH receptors with unparalleled affinity.

Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task.

Various lines of evidence suggest a role in cognition for the endogenous neuropeptide, neurotensin, involving an interaction with the central nervous system cholinergic pathways. A preliminary study has shown that central administration of neurotensin enhances spatial and nonspatial working memory in the presence of scopolamine, a muscarinic receptor antagonist which induces memory deficits. Utilizing similar methods, the present study employed a two-trial novel object discrimination task to determine the acute effect of a neurotensin peptide analogue with improved metabolic stability, PD149163, on recognition memory in Lister hooded rats.

Structure-activity studies with high-affinity inhibitors of pyroglutamyl-peptidase II.

Inhibitors of PPII (pyroglutamyl-peptidase II) (EC 3.4.19.

Central administration of thyrotropin releasing hormone (TRH) and related peptides inhibits feeding behavior in the Siberian hamster.

Centrally acting thyrotropin releasing hormone (TRH), independent of endocrine action, has been shown to regulate several metabolic and behavioral parameters in rats, including food intake and locomotor activity. The present study investigated and compared the effects of central TRH on feeding behavior in Siberian hamsters exposed to long (LP) or short (SP) photoperiods, which induce natural physiological states of obesity and leanness respectively. The effects of two TRH analogues, RX77368 (a metabolically stable TRH analogue) and TRH-Gly (an endogenous precursor to TRH with putative preferential action at the central TRH receptor, TRH-R2), were also investigated.