Histamine analogue

Bufotenidine or Cinobufagine This is the quaternary amine internal salt, 5-hydroxy-N,N,N-trimethyltryptammonium salt. It also is frequently found as a hydrogen sulfate ester, but this latter has no trivial name. Mention has been made of bufotenidine and its sulfate ester as a occasional companion of histamine analogues found in frog skins. See the appendix on histamines. 

The development of rigid histamine analogues is important for the determination of the H3 receptor pharmacophore as the conformations of these compounds only allow restricted spatial orientation of the imidazole ring with respect to the basic nitrogen in the side... 

Using a process similar to other 2-azaallenyl cyclizations, a number of novel histamine analogues have been made by applying the ring-chain transfer concept to the reaction of semicyclic 2-aza-3-methylthio-3-propeniminium iodides with methylamines possessing an acidic CH group [34 j. 

Betahistine-Betahistine is an orally active histamine analogue ( 0. 

It was necessary then to find out how histamine itself was binding to its receptors. Structure activity studies on histamine and histamine analogues revealed that the binding requirements for histamine to the HI and the proposed H2 receptors were slightly different. 

For the proposed H2 receptor, structure-activity studies were carried out to determine whether histamine analogues could bring about the physiological effects proposed for this receptor (e.g. stimulating gastric acid release). 

Figure 4. Structures of newly developed histamine analogues. The Hg receptor activity at the guinea-pig jejunum is indicated between parentheses. The dose-response curves for (R)-a-methylhistamine (RAMH), as measured as the inhibition of electrically-induced neurogenic contractions of the guinea-pig jejunum, in the absence or presence of three different concentrations of impentamine (VUF 4702) are shown.

As early as 1966, Ash and Schildd ), using a number of histamine analogues and several histamine-sensitive in vivo and in vitro preparations, succeeded in defining 2 distinct classes of histamine receptors (Hi and Hj ) certain of the agonists which they studied were more active at the former sites, others at the latter. The identification of these receptors in different organs is still far from complete. Some of the receptors thus far characterized are listed in Table 1. 

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