Formamidines receptor

Amidines. After the initial observation that formamidines are agonists for OA receptors in the firefly (14,15 58), these compounds have been shown to mimic OA in virtually every insect system known to contain OA receptors, including the DUMETi system (59)f the glandular lobe of the corpus cardiacum (60) and the fat body ( ) of the locust, and various CNS adenylate cyclase preparations (26-28). The structure-activity relations of amidines as octopaminergic agonists have been examined in several systems including adenylate cyclase stimulation in the firefly lantern and... 

A new H3 antagonist AQ 145 (N-l-adamantyi-N N [l,5-(3-4,(5)-lH imidazolyl)-petanediyl]formamidine dihydrochloride) was synthesized by Green Cross Pharmac. Co, Osaka, Japan. AQ 145 has 5-fold higher affinity to H3 receptors than thioperamide in in vitro binding assay. The effect of this compound on electrically-induced convulsions in mice was examined as similarly as described above. The durations of tonic, clonic and convulsive come phases were significantly decreased by i.p. administration of 30 mg/kg dose [6]. 

Dudai, Y., Buxbaum, J., Corfas, G., and Ofarim, M., Formamidines interact with Drosophila octopamine receptors, alter the flies behavior, and reduce their learning ability, /. Comp. Physiol., 161 A, 739,1987. 

More recently, Chen et al. (2007) found two amino acid substitutions (T8P, L22S) in a putative octopamine receptor in amitraz-resistant cattle ticks. Thus, point mutations may play a role in resistance to formamidine pesticides in ticks. 

Compounds that alter insect behavior in other ways may also be useful e.g. chemicals that increase insect locomotor activity should enhance the uptake of pesticides from treated surfaces. Such compounds are already known among the formamidines insecticides and their relatives that stimulate octopamine receptors (12), and further research in this area of pest biochemistry could reveal other locomotor stimulators such as phosphodiesterase inhibitors. A... 

Interest in octopamine receptors has grown with the discovery that a novel group of pesticides, the formamidines, are octopamine agonists (95). Thus chlordimeform (CDM) or demethylchlordimeform (DCDM) are able to activate octopamine receptors in firefly lantern (95,96), tobacco hornworm central nervous system (88), locust skeletal muscle (97), locust oviduct muscle (91,), locust corpora cardiaca (98), locust fat body (99). and cockroach haemocytes (39). 

Our agonist studies were designed to further document the effect of lower doses of OA on male sensitivity to pheromone (as shown in Figure 1), and to provide a pharmacological profile that could be compared with data from other published studies on OA receptors (12-14). The compounds included 1) the phenylethylamines synephrine and dopamine, 2) the formamidine chlordimeform, and 3) the substituted imidazolines naphazoline (2-[ 1-naphthylmethyl] imidazoline ), lofexidine (2-[ l-(2,6-dichlorophenoxy)ethyl]-2-imidazoline), XAMI (2,3-xylylaminomethyl-2-imidazoline), clonidine (2-(2,6-dichloro-anilino)-2-imidazoline), tolazoline (2-benzyl-2-imidazoline), and tramazoline (2-[5,6,7,8-tetrahydro-1-naphthyl]amino-2-imidazoline) ... 

The stimulation of the octopaminergic nervous system of invertebrates is a proven strategy for the control of important pest species. This has been achieved in the past by the use of octopamine receptor agonists such as formamidine and imidazoline derivatives. However, other potential strategies to achieve this end include the inhibition of cyclic nucleotide phosphodiesterase, inhibition of the neural reuptake of octopamine, and inhibition of octopamine N-acetyltransferase. Using the American cockroach nervous system, formamidines were found to inhibit both the uptake and acetylation of octopamine, but not with a potency comparable to their effect on octopamine receptors. The tricyclic antidepressant, desipramine, and the benzylamine, xylamine, were the most active inhibitors of these octopamine removal systems. The pharmacological profiles for uptake and N-acetylation appear to be quite similar, but differ from that of the adenylate cyclase-linked octopamine receptor. 

Formamidines (such as chlordimeform (Figure 1) and amitraz) and imidazolines (such as naphazoline and XAMI Figure 1) cause a series of behavioral and lethal effects in insects and acarines that may be ascribed entirely or in part to the actions of these compounds and their common metabolites as powerful agonists at octopamine receptors... 

A modification to this reaction can be seen in the reaction of a dicarbonyl equivalent, acyl-vinyl-phosphonium salt. Reaction of the phosphonium salt with an appropriately functionalized formamidine provides the imidazole phosphonium salt. The imidazole phosphonium salt can be further functionalized to an intermediate used to synthesize the cimetidine, an H2-receptor histamine antagonist used to treat ulcers. 

Expression of a Bombyx mori Tyramine Receptor in HEK-293 Cells and Action of a Formamidine... 

---