Zolantidine (SK&F 95282) is a potent selective brain‐penetrating histamine H2‐receptor antagonist

  title={Zolantidine (SK\&F 95282) is a potent selective brain‐penetrating histamine H2‐receptor antagonist},
  author={C. R. Calcutt and Charon Robin Ganellin and Roger Griffiths and B. K. Leigh and Jacqueline Maguire and Robert C. Mitchell and M. E. Mylek and M E Parsons and Ian R. Smith and R. C. Young},
  journal={British Journal of Pharmacology},
1 The novel benzthiazole derivative zolantidine (SK&F 95282) is a potent antagonist of histamine at H2‐receptors in guinea‐pig atrium and rat uterus. Only apparent pA2 values of 7.46 and 7.26 respectively could be calculated since the slopes of the Schild plots were significantly less than unity. 2 Zolantidine is equally potent as an antagonist at histamine H2‐receptors in guinea‐pig brain. The compound inhibited histamine stimulated adenylate cyclase (pKi 7.3) and dimaprit stimulated adenosine… 

Cardiac and gastric effects of histamine H2 receptor antagonists: no evidence for a correlation between lipophilicity and receptor affinity

Results obtained in this study showed that the discrepancies between gastric and cardiac effects observed for some H2 antagonists are not explained solely by differences in lipophilicity of compounds, and suggests that ionization has a similar influence for all the molecules on the partition between the lipophilic and aqueous phase.

Pharmacological Characterization and Autoradiographic Localization of Histamine H2 Receptors in Human Brain Identified with [125I]Iodoaminopotentidine

The widespread distribution of H2 receptors in the human brain is consistent with the alleged modulatory role of histamine mediated by this subtype of receptor.

Effects of histamine H2 receptor agonists and antagonists on the isolated guinea pig gallbladder

In conclusion, histamine H2 receptors in guinea pig gallbladder resemble those of the heart, as regards their sensitivity to zolantidine and compound SKF 92857, which, by contrast, were unable to antagonize histamine effects at gastric H 2 receptors in different experimental models.

Histamine H2‐like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [3H]tiotidine binding

Chick cerebral cortex contains H2‐like HA receptors that are linked to the cAMP‐generating system and are labelled with [3H]tiotidine, a selective H2 antagonist, and it is suggested that the studied receptors represent either an avian‐specific H 2‐like ha receptors or a novel subtype of HA receptors.

Psychomotor stimulant effects of the stereoisomers of chlorpheniramine

  • J. Bergman
  • Biology, Psychology
  • 2005
These findings suggest that the psychomotor stimulant effects of chlorpheniramine involve actions other than the blockade of histamine H1 or H2 receptors, and possibly mediate behavioral effects common to H1 antagonists and cocaine.



Pharmacological studies with SK&F 93944 (temelastine), a novel histamine H1‐receptor antagonist with negligible ability to penetrate the central nervous system

SK&F 93944 may have an advantage over classical histamine H1‐receptor antagonists in that it is likely to be devoid of untoward effects on the central nervous system.


The distribution of histamine H1 receptors, defined by the promethazine‐sensitive binding of [3H]mepyramine, in 11 different brain regions was uneven with the largest amounts in cerebellum, superior and inferior colliculus and hypothalamus and the smallest in caudate nucleus, brain stem and spinal cord.

Pharmacological Assay of Cardiac H2-Receptor Blockade by Amitriptyline and Lysergic Acid Diethylamide

Investigation of histamine responses of tachycardia in guinea pig right atrium and increased isometric tension in papillary muscle concludes that BOL, D-LSD, and amitriptyline are competitive antagonists of H-2-receptors in pharmacological assays, but other actions of these drugs distort or mask their measurement of H1-receptor affinity.

Inhibition of Histamine Synthesis in Brain by α‐Fluoromethylhistidine, a New Irreversible Inhibitor: In Vitro and In Vivo Studies

a‐Fluoromethylhistidine (α‐FMH), a new potent inhibitor of histidine decarboxylase (HD), has been used for in vitro and in vivo studies of brain HD. Following a preincubation with (+)‐α‐FMH, brain HD

Pharmacological specificity of brain histamine H2-receptors differs in intact cells and cell-free preparations

A test specific for H2-receptors is developed consisting of the stimulation of cyclic AMP accumulation by impromidine, a potent and highly selective H1-receptor agonist, in slices from guinea pig hippocampus and using it finds that H 2-receptionors differ considerably in their drug discriminatory properties from those mediating the stimulating of adenylate cyclase activity in homogenates.

3H-Glycogen hydrolysis elicited by histamine in mouse brain slices: selective involvement of H1 receptors.

3H-Glycogen synthesized in mouse cortical slices from 3H-glucose is hydrolyzed in a concentration-dependent manner by histamine with an EC50 of 3·10-6 M, suggesting that the maximal response is elicited when H1 receptors are only partially occupied.

Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor

It is shown here that histamine inhibits its own release from depolarized slices of rat cerebral cortex, an action apparently mediated by a class of receptor (H3) pharmacologically distinct from those previously characterized, that is, the H1 and H2 receptors.

Tricyclic antidepressant drugs block histamine H2 receptor in brain

To test this hypothesis, four tricyclic antidepressants—representing four different structural types—were tested on the H2 receptor linked to adenylate cyclase in homogenates of the guinea pig hippocampus and cortex.

Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes

It is concluded that [3H]‐baclofen or [3h]‐GABA are both ligands for the same bicuculline‐insensitive, divalent cation‐dependent binding sites in the rat brain.


Methylation was the major route of histamine catabolism in mouse brain and some of the methylhistamine formed was destroyed by monoamine oxidase, and no evidence for catabolisms by the action of diamine oxidase was found.