Pharmacology and Clinical Use of Pempidine in the Treatment of Hypertension

Harington, M.; Kincaid‐Smith, Priscilla; Milne, M. D.

doi:10.1016/s0140-6736(58)90002-3

Cited by 33 publications

(12 citation statements)

References 15 publications

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“…Similarly, Moos & Richard (1975) showed that intraventricular hexamethonium, in the conscious rat, blocked milk ejection (as measured by the weight gain of the young). Mecamylamine was, as expected, the more effective drug for being a secondary amine and lipid soluble it readily gains access to the brain (Harington, Kincaid-Smith & Milne, 1958), whereas the access of the more highly ionized drug hexamethonium (Dollery, 1964) would be more restricted. We see no evidence to implicate the fall in blood pressure produced by these nicotinic antagonists with the inhibition of the milk-ejection reflex, for no inhibition was observed with a variety of other vasodepressor substances.…”

Section: Discussionsupporting

confidence: 55%

Effects of Chounoceptor Antagonists on the Suckling‐induced and Experimentally Evoked Release of Oxytocin

Clarke

Fall

Lincoln

et al. 1978

British J Pharmacology

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1 In the anaesthetized lactating rat, the suckling of the young causes the regular release (about every 7 min) of brief pulses of oxytocin (0.5 to 1.0 mu), which each produce a single transient increase in intramammary pressure.2 The effects of several cholinoceptor antagonists were studied in relation to this natural reflex, and also the release of oxytocin evoked by the intraventricular injection of cholinomimetics. 3 Reflex milk ejection was blocked by the nicotinic antagonists mecamylamine and hexamethonium, and the inhibition was dose-dependent (ED50 of 1 mg/kg i.v. and 5 mg/kg i.v., respectively). Despite the use of high doses, the muscarinic antagonists atropine (200 mg/kg), hyoscine (90 mg/kg) and benzhexol (30 mg/kg) all failed to prevent the reflex release of oxytocin. The release of oxytocin by intraventricular bethanechol or carbachol was abolished by atropine (0.1 to 1.0 mg/kg) but not by mecamylamine (5 mg/kg) or hexamethonium (5 mg/kg). 6 None of the antagonists used significantly affected either the release of oxytocin following electrical stimulation of the neurohypophysis or the mammary sensitivity to endogenous or exogenous oxytocin. 7 The results suggest that the neural pathway controlling the reflex release of oxytocin during suckling in the rat contains a cholinergic component, which acts through nicotinic receptors. A second cholinergic pathway, of the muscarinic type, may also exist. The role of these two pathways is discussed.

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Section: Discussionsupporting

confidence: 55%

Effects of Chounoceptor Antagonists on the Suckling‐induced and Experimentally Evoked Release of Oxytocin

Clarke

Fall

Lincoln

et al. 1978

British J Pharmacology

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“…Harrington, Kincaid-Smith & Milne (1958) have shown that both pempidine and mecamylamine can be extracted from brain tissue after intraperitoneal injection in the rat. It is also likely that the effects of calcium chloride and central vagal stimulation are exerted in the central nervous system so that inhibition of their effects by Pratesi's compounds is probably a central effect.…”

Section: Resultsmentioning

confidence: 99%

The Effects of Drugs on the Release of Vasopressin

Dyball

1968

British Journal of Pharmacology and Chemotherapy

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“…However, there is evidence (Harington, Kincaid-Smith and Milne, 1958) that pempidine exhibits less protein-binding than does mecamylamine and this will undoubtedly modify its distribution and excretion pattern, and hence its duration of action. Blood and urine levels in both rats (Reading, personal communication) and patients have shown that pempidine is excreted more rapidly than mecamylamine and in clinical use pempidine has been found to have a less prolonged action than mecamylamine (Harington et al, 1958).…”

Section: T-oxicitymentioning

confidence: 99%

Pharmacological Properties of Pempidine (1:2:2: 6: 6‐pentamethylpiperidine), a New Ganglion‐blocking Compound

Corne

Edge

1958

British Journal of Pharmacology and Chemotherapy

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Pempidine (1: 2: 2: 6: 6-pentamethylpiperidine) is a long-acting ganglion-blocking compound which is effective by mouth. By intravenous injection it has a similar potency to hexamethonium on the preganglionically stimulated nictitating membrane of the cat. The compound blocks the effects of intravenous nicotine and of peripheral vagal stimulation on the blood pressure; it also causes dilatation of the pupil after removal of the sympathetic innervation. On the guinea-pig ileum, the predominant effect of the compound is to inhibit nicotine contractions. Pempidine is well absorbed from the gastro-intestinal tract as judged by (a) the low ratio (6.9) of oral to intravenous toxicities, (b) the rapid development of mydriasis in mice after oral administration of small doses, and (c) the rapid onset of hypotension when the compound is injected directly into the duodenum of anaesthetized cats. Other actions include neuromuscular paralysis of curare-like type when large doses of the compound are injected intravenously and central effects such as tremors which occur with near toxic doses. In cats with a low blood pressure, large intravenous doses have a slight pressor action.

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Pharmacology and Clinical Use of Pempidine in the Treatment of Hypertension

Cited by 33 publications

References 15 publications

Effects of Chounoceptor Antagonists on the Suckling‐induced and Experimentally Evoked Release of Oxytocin

Effects of Chounoceptor Antagonists on the Suckling‐induced and Experimentally Evoked Release of Oxytocin

The Effects of Drugs on the Release of Vasopressin

Pharmacological Properties of Pempidine (1:2:2: 6: 6‐pentamethylpiperidine), a New Ganglion‐blocking Compound

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