Yohimbine antagonism of the vasodepression elicited by organophosphates applied on ventral medulla oblongata.
The rostral ventral surface of medulla oblongata (RVMO) has been shown to constitute a selective target for organophosphate (op) cholinesterase inhibitors. The action of soman (S) as compared with (7-nitrobenz-2-oxa-1,3 diazole)aminopentyl methylphosphonofluoridate (NBD-AP-MPF), a fluorescent organophosphate has now been examined in anesthetized cats pretreated with atropine sulphate. Blood pressure (BP), electrocardiogram (ECG) and respiration (R) were recorded. In some animals a cannula was implanted into the right lateral ventricle. Chemicals were bilaterally applied on RVMO by means of a perspex cannula and removed after 5 min. The application of 2.5 micrograms S or 60 micrograms NBD-AP-MPF elicited severe fall of BP which recovered only after 2 h in the case of the former and up to 45 min in the latter. Smaller doses produced corresponding responses of lesser magnitude. Accompanying R changes consisted in most cases of increased rate and reduced amplitude whereas in others the opposite or mixed alterations occurred. Frequently, sigh-like movements intermingled at periodic intervals with regular R deflections. The sighs were interpreted as aiming to correct blood gases balance. After application of atropine on RVMO--but not by systemic administration--BP and R were restored whereas single repeated i.v. injection of 1 microgram/kg noradrenaline produced only transient reversals without influencing the course of long lasting vasodepression. In contrast, the intraventricular administration of 250-500 micrograms yohimbine considerably reduced both the magnitude and extent of the vasodepression elicited by topically applied organophosphates. It is postulated that central alpha 2-adrenoceptors in contrast to vascular sites are likely involved in the op-induced vasodepression. The present work provides an indication that effective antagonists might be developed considering blockade of these receptors.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004562:Electrocardiography; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors*; D012119:Respiration / Q000187:drug effects; D012524:Sarin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012999:Soman / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D015016:Yohimbine; D001285:Atropine; C039469:5-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)pentyl methylphosphonofluoridate; D012999:Soman; D012524:Sarin; D009638:Norepinephrine