Effect of formamidines on 5-hydroxytryptamine uptake and biogenic amine levels in rat platelets.
Uptake of radioactive 5-hydroxytryptamine (5-HT) by platelets from rats treated intraperitoneally with the insecticide/acaricide chlordimeform (CDF) at 25 mg/kg was not significantly influenced at 1 h; however, uptake of this amine by platelets from rats treated with its N- monodemethyl metabolite (DMC) at the same dosage was significantly inhibited (37%). Two reversed phase high performance liquid chromatographic systems with electrochemical detection were developed with a capacity to separate 11 biogenic amines and related compounds. Only 5-HT, norepinephrine (NE), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were consistently detected in platelets and plasma samples. At 1 h and/or 24 h postinjection, CDF effected significant decreases in platelet levels of 5-HT, NE, and DA and plasma levels of 5-HT, whereas platelet and plasma levels of DOPAC were significantly increased. DMC effected significant decreases in both platelet and plasma levels of 5-HT. These in vivo studies confirmed previous in vitro experiments which demonstrated that formamidines inhibited uptake of 5-HT by platelets and released endogenous stores of amines from platelets.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood; D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002742:Chlorphenamidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010575:Pesticides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000097:blood*
D000578:Amidines; D001679:Biogenic Amines; D010575:Pesticides; D015102:3,4-Dihydroxyphenylacetic Acid; C011741:demethylchlordimeform; D012701:Serotonin; D002742:Chlorphenamidine; D004298:Dopamine; D009638:Norepinephrine