Imidazole-substituted analogues of TRH limit behavioral deficits after experimental brain trauma.

Treatment with thyrotropin releasing hormone (TRH) or TRH analogues improves outcome after experimental brain or spinal cord trauma. TRH analogues with modifications at the N-terminal position of the tripeptide are effective, whereas analogues with modifications of the C-terminal residue are not. Imidazole-substituted TRH analogues, which modify the middle amino acid (histidine) of the tripeptide, have more recently been developed but have not been evaluated in models of central nervous system (CNS) trauma.

Biological activities of thionated thyrotropin-releasing hormone analogs.

Analogs of thyrotropin-releasing hormone (Glp-His-Pro-NH2, TRH) have been prepared which contain thioamide moieties in the pyroglutamic acid ring, the carboxyamide proline terminus, and in both positions (dithio). These compounds have been tested for TSH-releasing activities (in vitro and in vivo), and for binding to TRH receptors in rat pituitary and cortex. The monothionated analogs showed no significant differences in TSH-releasing potency from TRH either in vitro or in vivo.

Direct electrophilic fluorination of tyrosine in dermorphin analogues and its effect on biological activity, receptor affinity and selectivity.

In a preliminary communication we reported [(Tetrahedron Lett. 31, 619 (1990)] that acetyl hypofluorite can be used efficiently to introduce fluorine regiospecifically (ortho to OH) into the phenolic ring of tyrosine-containing peptides. This procedure has been applied to the fluorination of a number of mu-selective opioid peptides derived from dermorphin.

Selective cardiorespiratory activity of an iodinated analog of thyrotropin-releasing hormone (TRH).

The biological activity of thyrotropin-releasing hormone (TRH) and its analogs 4(5)-I-Im-TRH and 2,4(5)-I2-Im-TRH was assessed by means of their effects on: 1) the mean arterial pressure (MAP), 2) heart rate (HR), 3) ventilation minute volume (MV), 4) contractility of the rat duodenum, and 5) concentrations of thyrotropin (TSH) or prolactin (PRL) in serum. Also their binding to TRH-receptors in brain homogenates was studied. In urethane-anesthetized rats TRH ICV increased MAP, HR and MV.

Norvaline2-TRH: binding to TRH receptors in rat brain homogenates.

Norvaline2-thyrotropin-releasing hormone ([Nva2]TRH) has been described as a thyrotropin-releasing hormone (TRH) analog with no thyrotropin (TSH)-releasing capacity but enhanced analeptic activity compared with TRH, as shown by the reversal of haloperidol-induced catalepsy. We have evaluated the receptor-binding properties of [Nva2]TRH in homogenates of rat anterior pituitary, hypothalamus, brainstem and cortex tissue, using [3H]TRH and [3H][3-Me-His2]TRH as radioligands. Apparent Ki values at high affinity TRH-binding sites, labelled predominantly by [3H][3-Me-His2]TRH, ranged from 17.