Pharmacological effects of MDL 11,939: A selective, centrally acting antagonist of 5‐HT2 receptors

  title={Pharmacological effects of MDL 11,939: A selective, centrally acting antagonist of 5‐HT2 receptors},
  author={Mark W. Dudley and Norbert L. Wiech and Francis P. Miller and Albert Anthony Carr and Hsien Chang Cheng and Lawrence E. Roebel and Niall Stephen Doherty and Henry I. Yamamura and Richard C. Ursillo and Michael G. Palfreyman},
  journal={Drug Development Research},
MDL 11,939 (α‐phenyl‐1‐(2‐phenylethyl)‐4‐piperidine methanol) has been shown, through in vitro studies utilizing radioligand binding and isolated tissues as well as through in vivo tests of central and peripheral serotonergic activity, to be a potent, selective antagonist at 5‐hydroxytryptamine receptors of the 5‐HT2 subtype. In particular, MDL 11,939 shows low affinity for the 5‐HT1 and 5‐HT3 subtypes of the serotonin receptor and displays low or negligible affinity for alpha adrenergic… 

Contractile 5‐HT1 receptors in human isolated pial arterioles: correlation with 5‐HT1D binding sites

It is concluded that a 5‐HT1‐like receptor, which shares strong similarities with the 5‐ HT1D binding sites identified in human caudate membranes, is mediating the vasocontractile action of 5-HT in human pial arterioles.

Antagonism of 5-hydroxytryptamine(2a) receptors attenuates the behavioral effects of cocaine in rats.

It is suggested that 5-HT2A receptors play an important role in the behavioral effects of cocaine and that they should be considered a viable target for analysis in the search for pharmacotherapies useful in the treatment of cocaine dependence.

Centrally active 5-HT receptor agonists and antagonists

Efficacy trial of the 5-HT2 antagonist MDL 11,939 in patients with generalized anxiety disorder.

MDL 11,939 was well tolerated but did not demonstrate significant anxiolytic effects in this pilot study, and the incidence of adverse events between treatments was similar.

The influence of 5‐HT2 and 5‐HT4 receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test

It was concluded that in BKW mice the failure of 5‐HT2 and5‐HT4 receptor antagonists when administered alone to modify behaviour in the light/dark test indicates an absence of an endogenous 5‐ht tone at the 5‐ HT2 and 5-HT4 receptors.



Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT

3H-PAT seems to be a useful ligand for studying the biochemical and pharmacological characteristics of presynaptic autoreceptors in selected regions of rat brain.

Characteristics of central 5-HT receptors and their adaptive changes following intracerebral 5,7-dihydroxytryptamine administration in the rat.

Lysed synaptosomal (P 2 ) fractions from adult rat brain were extensively washed and incubated in such a way that most bound 5-HT was eliminated, and the characteristics of the binding sites for [ 3 H]dihydroalprenolol and [3 H]haloperidol in the hippocampus and the striatum, respectively, were altered by 5,7-HT treatment.

5-Hydroxytryptamine receptor in rabbit aorta: characterization by butyrophenone analogs.

The contractile response of isolated rabbit aorta rings to 5-hydroxytryptamine (5-HT) was antagonized by spiperone and four other butyrophenone analogs in a competitive manner, suggesting a congruence between the aortic "D" receptors and 5-HT2 type binding sites in rat brain.

Antagonists of Histamine, 5-Hydroxytryptamine and SRS-A

Compounds that selectively inhibit histamine-induced gastric secretion and other effects of histamine resistant to the earlier antihistamines were first reported only in 1972 by Black and colleagues and are referred to as antagonists at H2 receptors, in distinction from the earlierantihistamines.

Contractile serotonergic receptor in rat stomach fundus.

Neither the potency nor maximum response of these agonists in contracting the rat stomach fundus correlated with the affinity of agonists at 5HT1A, 5Ht1B or5HT1C binding sites, suggesting that these agents have little, if any, affinity for the serotonergic receptor-mediating contraction in the fundus.

Mechanism of the Hypotensive Effect of Ketanserin

  • J. Fozard
  • Biology, Medicine
    Journal of cardiovascular pharmacology
  • 1982
D doses of ketanserin that lower blood pressure in anesthetized normotensive rats and in conscious SHR inhibit sympathetic tone to the peripheral vasculature by blocking α1-adrenoceptors under the conditions of these experiments.