Physiological Effects of Alkyl Polyphosphates

Burgen, A. S. V.; Keele, C. A.; Chennells, Mary; Castillo, Juan; Floyd, W. F.; Slome, D.; Wright, Samson

doi:10.1038/160760a0

Cited by 21 publications

(11 citation statements)

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“…In most species, the effect of systemic intoxication with an anti-cholinesterase-for example, HETP (hexaethyltetraphosphate), TEPP (tetraethyl pyrophosphate), dyflos (diisopropylphosphorofluoridate), Tabun (ethyl NN-dimethylphosphoramidocyanidate), or neostigmine-is predominantly the production of a profound fall in blood pressure (Modell, Krop, Hitchcock and Riker, 1946;Heymans and Jacob, 1947;Lundholm, 1949;Burgen, Keele and Slome, 1949;Verbeke and Votava, 1949;Salerno and Coon, 1949;Holmstedt, 1951). We have recently noticed that the intravenous administration of the anti-cholinesterase " Sarin " (isopropyl methylphosphonofluoridate) to intact rats produces a sharp rise in blood pressure, then one or two oscillations about the point of increased pressure, followed by a very gradual fall in pressure over the next several minutes (10-180 min. in different animals) back to the pre-injection level (Fig.…”

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The Effect of Anti‐cholinesterase Agents on the Rat's Blood Pressure

Dirnhuber¹,

Cullumbine²

1955

British Journal of Pharmacology and Chemotherapy

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In most species, the effect of systemic intoxication with an anti-cholinesterase-for example, HETP (hexaethyltetraphosphate), TEPP (tetraethyl pyrophosphate), dyflos (diisopropylphosphorofluoridate), Tabun (ethyl NN-dimethylphosphoramidocyanidate), or neostigmine-is predominantly the production of a profound fall in blood pressure (Modell, Krop, Hitchcock and Riker, 1946;Heymans and Jacob, 1947;Lundholm, 1949;Burgen, Keele and Slome, 1949;Verbeke and Votava, 1949;Salerno and Coon, 1949;Holmstedt, 1951). We have recently noticed that the intravenous administration of the anti-cholinesterase " Sarin " (isopropyl methylphosphonofluoridate) to intact rats produces a sharp rise in blood pressure, then one or two oscillations about the point of increased pressure, followed by a very gradual fall in pressure over the next several minutes (10-180 min. in different animals) back to the pre-injection level (Fig. 1). The cause of this sustained rise in blood pressure produced by sarin has been investigated. METHODSWhite rats of homogeneous strain and weighing 350-500 g. were used. They were anaesthetized with urethane (1.25 g./kg. subcutaneously), and polythene cannulae were inserted into the carotid artery, to record blood pressure, and into the femoral vein. (Fig. 2). With higher single doses (e.g. 90 Itg./kg.) the animal dies before the sustained rise in blood pressure has become established.Bilateral vagotomy does not affect the results, but if sarin is given to a spinal rat only a relatively slow, small and short-lasting increase in blood pressure is caused (Fig. 3). The failure of sarin to produce a sustained elevation of blood pressure in this experiment is not due to the low blood pressure presented by a spinal rat.

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The Effect of Anti‐cholinesterase Agents on the Rat's Blood Pressure

Dirnhuber¹,

Cullumbine²

1955

British Journal of Pharmacology and Chemotherapy

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“…The anti-curari action of HETP demonstrated by Burgen et al (1949) on the rat-isolated phrenic nerve-diaphragm preparation can readily be shown in cat muscle receiving its normal blood supply. In Fig.…”

Section: Effects Of Hetp and Teppmentioning

confidence: 95%

“…In this paper we shall describe the action of these drugs on the nerve-muscle response and on certain reflexes in the cat. The actions of the drugs on other systems are fully described by Burgen, Keele & Slome (1949).The exact constitution of HETP is at present uncertain. It is known to be a mixture of ester phosphates, polyphosphates and perhaps metaphosphates.…”

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“…The drugs used were injected intravenously (into the central end of the jugular vein), intraarterially (into the central end of the inferior mesenteric or iliac arteries (Wilson & Wright, 1936-7), or intrathecally (Calma & Wright, 1947) approximately at the level of the seventh lumbar vertebra. The HETP and TEPP were diluted with saline just before being injected; in some experiments the dilutions were made from the original liquid, and in others from a 1% stock solution of the drug in propylene glycol.…”

Section: Chennells W F Floyd and S Wright-mentioning

confidence: 99%

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Action of condensed alkyl phosphates on the nerve‐muscle preparation and the central nervous system of the cat

Chennells¹,

Floyd²,

Wright³

1949

The Journal of Physiology

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A preliminary report on the general pharmacological actions of two condensed alkyl phosphates, hexaethyltetraphosphate ('HETP') and tetraethylpyrophosphate ('TEPP') has already been published (Burgen, Keele, Chennells, del Castillo, Floyd, Slome & Wright, 1947); details about the chemical properties of the drugs were communicated by Topley (1947). In this paper we shall describe the action of these drugs on the nerve-muscle response and on certain reflexes in the cat. The actions of the drugs on other systems are fully described by Burgen, Keele & Slome (1949).The exact constitution of HETP is at present uncertain. It is known to be a mixture of ester phosphates, polyphosphates and perhaps metaphosphates. On solution in water an immediate hydrolysis occurs and it is possible that triethylpyrophosphate is formed and is the physiologically active molecule. A further slow hydrolysis occurs forming equimolecular proportions of monoethyl phosphoric and diethyl phosphoric acids, which are physiologically inert. Other workers (Hall & Jacobson, 1948)

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Poisoning Due to Tetraethylpyrophosphate

Faust¹

1949

JAMA

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ALLERGENICITYTo determine the human sensitivity to bacitracin, ISO adults were patch tested with bacitracin ointment (1,000 units per gram of petrolatum) for forty-eight hours. All tested areas were negative for reaction.A fortnight later, 50 of these previously tested persons were retested by the patch method on the same or approximate sites for another forty-eight hour period. All test sites were again normal after the patches were removed.These results seemed indicative of low allergenicity and were subsequently corroborated by the occurrence of only 1 case of dermatitis of the contact type among the 138 patients subsequently treated with bacitracin ointment. This unique patient was not only allergic to the ingredients of bacitracin ointment (bacitracin and petrolatum) but also reacted violently to liquid petrolatum, soybean oil bases, olive oil, wool fat, lard,

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Physiological Effects of Alkyl Polyphosphates

Cited by 21 publications

References 4 publications

The Effect of Anti‐cholinesterase Agents on the Rat's Blood Pressure

The Effect of Anti‐cholinesterase Agents on the Rat's Blood Pressure

Action of condensed alkyl phosphates on the nerve‐muscle preparation and the central nervous system of the cat

Poisoning Due to Tetraethylpyrophosphate

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