The importance of lipid-solubility for the central action of cholinolytic drugs

Herz, A.; Teschemacher, H.; Hofstetter, Amelia R.; Kurz, Herbert

doi:10.1016/0028-3908(65)90037-7

Cited by 88 publications

(18 citation statements)

References 7 publications

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“…It is known however that in the periphery the potencies of atropine and methylatropine me different. Peripherally administered atropine is about 2.8 times less effective than methylatropine [11]. The higher inhibition by methylatropine may be attributed also to a higher leakage of atropine from the brain into the blood [1].…”

Section: Discussionmentioning

confidence: 94%

Central blockade of (methyl-)atropine on carbachol drinking: A dose-response study

Terpstra

Slangen

1972

Physiology & Behavior

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TERPSTRA, G. K. AND J. L. SLANGEN. Central blockade of(methyl-) atropine on carbachol drinking: a dose-response study. PHYSIOL. BEHAV. 8 (4) 715--719, 1972. Administration of carbachol in the tractus diagonalis in rats elicited drinking and no eating. Norepinephrine administered in the same place did not induce drinking or eating. The specific drinking response induced by stimulation with 7.2 nmol (= 1.3 ~tg) of carbachol was gradually inhibited by preceding injections of graded doses of atropine and methylatropine at the same site. A 90 % inhibiting action of atropine and methylatropine was possible with a 3-10 times lower dose (0.18 ~tg) than used in earlier studies. Significant differences between the inhibition by atropine and methylatropine could not be demonstrated. A possible difference in inhibition at the lowest dose of atropine and methylatropine used (= 0.04 p~g) was discussed. Water intakeCarbachol stimulation Dose-response relationship Tractus diagonalisAtropine Methylatropine LOCAL stimulation of different parts of the limbic system of the rat with cholinergic substances, like carbachol and acetylcholine, elicits water drinking in water satiated rats [4,7,8].A dose response curve for the water intake elicited by injection of carbachol in the feeding-drinking area of the hypothalamus has been established. A maximal intake of water occurred after administration of 2.4 × 10-°M of carbachol (= 0.4 ~g)[16]. Levitt et aL [15] found for a number of different structures a maximal effect with a dose of 1 ~g of carbachol. Detailed observations have been made concerning the role of the preoptic and septal area in the elicitation of drinking behavior after local administration of carbachol [3,5,14].Carbachol-elicited drinking was inhibited by atropine when administered systemically [9,18]. On the other hand atropine not only blocked the effect of carbachol when administered in the same brain region as carbachol [9,14,19], but also when administered in another brain region in the limbic system [14].On the assumption that drinking elicited by carbachol is the result of activation of a cholinergic system, atropine, administered peripherally as well as centrally, has been used by several authors in order to block the effects of carbachol administered in the septal area. These results have been obtained by using about equal dosages of carbachol and atropine (tzg). It is not known however whether these doses of atropine axe likely to block only the stimulated parts of the cholinergic drinking system or other cholinergic systems affecting behavior as well. To answer that question information about the dose response relationship of carbachol elicited drinking and atropine is needed. To investigate this relationship in all areas of the limbic system that are supposed to play a role in the regulation of water intake is simply prohibiting. In our experiments we therefore concentrated on the anterior part of the preoptic area which is believed to be a part of the limbic drinking circuit [5].The purpose of the following ...

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Section: Discussionmentioning

confidence: 94%

Central blockade of (methyl-)atropine on carbachol drinking: A dose-response study

Terpstra

Slangen

1972

Physiology & Behavior

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“…They did not measure breathing or EEG during those episodes, so it is not known whether the bradycardia occurred during seizures Quaternary ammonium derivatives of muscarinic receptor antagonists, such as methylatropine and N-methylscopolamine, are used as selective antagonists of peripheral muscarinic receptors, as they are less likely to penetrate the blood-brain barrier (56,57). N-methylscopolamine (1 mg/kg, i.p.)…”

Section: Severe Peri-ictal Respiratory Dysfunction Is Common In Dravementioning

confidence: 99%

Severe peri-ictal respiratory dysfunction is common in Dravet syndrome

Kim¹,

Bravo²,

Thirnbeck³

et al. 2018

Journal of Clinical Investigation

112

168

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“…If necessary, quenching was avoided by dilution 1 : 10 or 1 : 20. Partition Coefficient Partition coefficients were determined at room temperature with the method of Herz et al [1965] using as organic phase /¡-heptane which is suitable for work aiming at penetration through the blood-brain barrier [Kurz and Appiah, 1969]. The watery phase was 1/15 M phosphate buffer (Soerensen) with the pH 7.4.…”

Section: Determination Of Alkaloidsmentioning

confidence: 99%

Cerebral Pharmacokinetics of Tremor-Producing Harmala and Iboga Alkaloids

Zetler¹,

Singbartl²,

Schlosser³

1972

Pharmacology

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Tremor-producing activity and concentration in brain were determined in mice for 4 harmala and 5 iboga alkaloids. All compounds were active, however, harmalol only after intracerebral injection. Kinetics of evasion from brain were first-order functions with most drugs, but revealed 2 compartments for harmalol and 3 for ibogaline. Tremor-producing activity was much more influenced by chemical structure than by lipid solubility. This points to specific receptors for indole compounds in tremorigenic brain structures.

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The importance of lipid-solubility for the central action of cholinolytic drugs

Cited by 88 publications

References 7 publications

Central blockade of (methyl-)atropine on carbachol drinking: A dose-response study

Central blockade of (methyl-)atropine on carbachol drinking: A dose-response study

Severe peri-ictal respiratory dysfunction is common in Dravet syndrome

Cerebral Pharmacokinetics of Tremor-Producing Harmala and Iboga Alkaloids

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