Pharmacological interest in the tripeptide thyrotropin-releasing hormone (TRH) 
is due to the multiple effects it produces. In fact, apart from taking part in 
regulating the activity of the hypothalamo-pituitary-thyroid axis, TRH produces 
various neuropharmacological effects which indicate a biological role that is 
probably more important than that of a releasing hormone. Trials performed in 
animals have shown, for example, the dose-dependent capacity of TRH to induce 
analgesia, probably by interacting with the opioid peptide system. Motor 
activity is affected by TRH. In fact this tripeptide elicits an increase in 
spontaneous motor and explorative activities by interacting with the 
dopaminergic neurotransmitter system at the nucleus accumbens level. The 
neuropharmacological activities of TRH include an interesting arousal effect and 
an analeptic action on generalized depression of the CNS whether this depression 
is of natural origin, such as hibernation, or induced pharmacologically 
(barbiturates, ethanol) or of a traumatic origin (coma). This analeptic action 
is attributable to stimulation of cholinergic neurons in the septo-hippocampal 
area and to the presence of terminals containing TRH in the lateral septum and 
TRH receptors concentrated especially in the medial septum and diagonal band of 
Broca. It has also been suggested that TRH localized in the pineal gland has a 
part in activating the neuronal mechanisms of arousal. Associated with the 
arousal effect and especially evident in variously originated shock conditions 
are the activating effects of TRH on vegetative functions (body temperature, 
circulation, the gastrointestinal tract). These stimulatory activities on the 
CNS were the rationale for therapeutic use of TRH in the initial treatment of 
coma due to brain trauma and for the treatment of endogenous depression. A most 
interesting property of TRH is that of counteracting the neurological deficit 
due to experimental lesion of the spinal cord particularly with regard to 
spasticity and ataxia. Electrophysiological trials have shown that TRH 
depolarizes the motoneurons in frog spinal cord thereby increasing the 
monosynaptic reflex. Furthermore, TRH has recently been shown to have a trophic 
effect on cultures of rat fetus spinal cord. On this basis TRH has been used 
successfully for the treatment of amyotropic lateral sclerosis (Charcot's 
syndrome) and spinocerebellar degeneration. Further support for this therapeutic 
strategy is given by the demonstration that deafferentiation of rat spinal cord 
produces an increased density of TRH spinal receptors. Recent studies have also 
given encouraging results on the possible therapeutic use of TRH for the 
treatment of Alzheimer's disease.(ABSTRACT TRUNCATED AT 400 WORDS)