Chlordimeform receptor

Animal studies have detected a variety of pharmacological and biochemical changes in response to chlordimeform exposure. The cause of death following acute exposure appears to be cardiovascular collapse. Chlordimeform interacts directly with and inhibits a2-adrenergic receptors in mammalian systems. Lethal doses of chlordimeform cause decreases in cardiac contractility and peripheral resistance resulting in severe hypotension. Respiratory arrest also occurs but is thought to be secondary to the cardiovascular effects. The effects of chlordimeform on the cardiovascular system share similarities with those seen with local anesthetics such as procaine. Chlordimeform also inhibits monoamine oxidase and acts as an uncoupler of oxidative phosphorylation. 

Chlordimeform elicits cardiovascular toxicity. a2-Adrenergic receptors are modulated in rat brain regions following systemic chlordimeform treatment. One study reported that chlordimeform influenced endocrine regulation within the reproductive system (decreased gonadotropin and testosterone levels) by disrupting hypothalamic a-adrenergic activity. 

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) ... 

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... 

---