1 : 2 : 2 : 6 : 6-Pentamethylpiperidine: a New Hypotensive Drug

Lee, G. E.; Wragg, W. R.; Corne, S. J.; Edge, N. D.; Reading, H. W.

doi:10.1038/1811717a0

Cited by 32 publications

(13 citation statements)

References 7 publications

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“…All compounds were well absorbed orally, as judged by the ratio of oral to intravenous LD50. In this respect, the results agree well with those on gastric secretion and with those of biochemical studies of Lee et al (1958). However, the ratio of oral to intravenous toxicity was somewhat lower for mecamylamine than for pempidine, which may therefore be less rapidly absorbed or more rapidly eliminated.…”

Section: Resultssupporting

confidence: 87%

“…Chronic Toxicity to Rats.-Preliminary tests in which pempidine, 26539, and mecamylamine were given by catheter once on each of 5 days a week for 2 weeks to groups of 6 rats, showed that the maximum tolerated daily dose of each was of the order of 50 mg./ kg. This dose caused loss of weight (see Lee et al, 1958) and condition, but did not kill any animals. Liver and kidney were unaffected by the drugs.…”

Section: Resultsmentioning

confidence: 98%

“…Determination of potencies of any of the three agents was therefore very difficult. Stone, Torchiana, Navarro, and Beyer (1956) and of Lee et al (1958), when the likely differences in conditions of measurement in three different laboratories are taken into account.…”

Section: Resultsmentioning

confidence: 99%

“…The values for mecamylamine are nearly identical with those given by Stone, Torchiana, Navarro, and Beyer (1956), but those for pempidine are higher than the values recently published by. Lee et al (1958).…”

Section: Resultsmentioning

confidence: 99%

“…The object of this report is to describe our development of the piperidines, which was different from that of Lee et al (1958), and to give a complete account of our pharmacological and toxicological studies of pempidine and 26539.…”

mentioning

confidence: 99%

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The Pharmacological Actions of Pempidine and Its Ethyl Homologue

Spinks¹,

Young²,

Farrington³

et al. 1958

British Journal of Pharmacology and Chemotherapy

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Pempidine, and other highly active ganglion blocking agents of the polyalkylpiperidine series, were developed from tertiary alkylamines, themselves weakly active, on the hypothesis that high activity was conferred by the presence in the molecule of a sterically hindered secondary or tertiary nitrogen atom. Pempidine and its n‐ethyl homologue (26539) resembled mecamylamine qualitatively. All three drugs blocked sympathetic and parasympathetic ganglia; this action was slow in onset and protracted. They blocked neuromuscular transmission, but only about one hundredth as powerfully as ganglionic transmission. They caused a fall in amplitude and rate of the isolated heart, and reduced coronary flow. They had local anaesthetic properties in one of four tests used. They caused tremor. All were well absorbed when administered orally. Pempidine was about twice as active as mecamylamine on ganglia, but only about one half to one quarter as toxic as judged by death, growth, induction of tremor, or cardiotoxicity. Compound 26539 was also quantitatively superior to mecamylamine in respect of these safety margins, but unlike pempidine or mecamylamine damaged the pituitary gland and testis when administered daily for several months. The mode of action of the three drugs is discussed: the results give tentative support for the hypothesis that their action is intracellular.

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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