JO 1784, a potent and selective ligand for rat and mouse brain σ‐sites

  title={JO 1784, a potent and selective ligand for rat and mouse brain $\sigma$‐sites},
  author={Francois J Roman and Xavier B. Pascaud and Brigitte Martin and D Vauch{\'e} and Jean Louis Junien},
  journal={Journal of Pharmacy and Pharmacology},
Abstract— JO 1784 ((+)‐cinnamyl‐1‐phenyl‐1‐N‐methyl‐N‐cyclopropylene) is a potent ligand for (+)‐[3H]SKF 10,047 (2′‐hydroxy‐5,9‐dimethyl‐2‐allyl‐6,7‐benzomorphan) binding sites in rat brain membrane preparations with an IC50 of 39 ± 8 nM, which is comparable to that of haloperidol. The stereoisomer of JO 1784 is ten fold less potent. When administered to mice i.p. or p.o. JO 1784 displaced (+)‐[3H]SKF 10,047 (5 μCi i.v.) from its sites in the brain with ID50 values of 1.2 and 3.5 mg kg−1… 

The σ ligand JO 1784 Prevents Trimethyltin‐Induced Behavioural and σ‐Receptor Dysfunction in the Rat

A neuroprotective effect of JO 1784 in the trimethyltin model would seem to be related to the modulatory effects of this sigma ligand on trimethyeltin-induced glutamate neurotoxicity.

The effects of sigma ligands and of neuropeptide Y on N‐methyl‐d‐aspartate‐induced neuronal activation of CA3 dorsal hippocampus neurones are differentially affected by pertussin toxin

This study provides the first in vivo functional evidence that sigma ligands and NPY modulate the NMDA response by acting on distinct receptors, differentiated by their PTX sensitivity.

Acute effects of Sigma ligands on the electrophysiological activity of rat nigrostriatal and mesoaccumbal dopaminergic neurons

It is concluded that acute sigma receptor occupation does not markedly alter the firing rate of DA neurons and the marked effects of certain sigma ligands on DA cell electrophysiology are likely due to their non‐sigma properties.

Central neuropeptide Y and the sigma ligand, JO 1784, reverse corticotropin‐releasing factor‐induced inhibition of gastric acid secretion in rats

NPY and JO 1784 (a sigma ligand) interacts with CRF in the PVN to block CRF‐induced inhibition of pentagastrin‐stimulated gastric acid secretion and is specific to CRF and may involve sigma binding sites.

The cytochromes P‐450 are not involved in the modulation of the N‐methyl‐D‐aspartate response by sigma ligands in the rat CA3 dorsal hippocampus

Two cytochrome P‐450 inhibitors, proadifen (SKF‐525A) and piperonyl butoxide (PB) have been tested in the model and found to prevent and suppress the potentiating effect of sigma agonists on the NMDA response.

Some of the effects of the selective sigma ligand (+)pentazocine are mediated via a naloxone‐sensitive receptor

Results suggest that the effects induced by some σ1 ligands may, in fact, be sensitive to naloxone while others may not, and the original classification of σ receptors as opiates might have been partly accurate.

Biphasic effects of sigma ligands on the neuronal response to N-methyl-D-aspartate

The potentiation of the NMDA response following the intravenous administration of a low dose of a σ ligand persisted for at least 60 min, after which point in time a second injection of the same dose induced the same degree of potentiation.

Modulation of serotonergic neurotransmission by short‐ and long‐term treatments with sigma ligands

A modulation of serotonergic neurotransmission by some sigma receptors is suggested and a potential mechanism for the ‘antidepressant effects’ reported is provided and evidence is provided toward sigma1 ligands as potential antidepressants with a rapid onset of action.



1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs.

Results indicate that [3H]Tol2Gdn is a selective ligand for the sigma-site, and should greatly facilitate the physiological, biochemical, and pharmacological characterization of sigma receptors in brain.

Pharmacological and autoradiographic discrimination of sigma and phencyclidine receptor binding sites in brain with (+)-[3H]SKF 10,047, (+)-[3H]-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine and [3H]-1-[1-(2-thienyl)cyclohexyl]piperidine.

Pharmacological and autoradiographic analyses reveal that (+)-[3H]SKF 10,047 labels two sites in brain: a high affinity site resembling the sigma receptor and a second site, labeled with lower affinity, similar to the phencyclidine (PCP) receptor.

(+)-[3H]SK&F 10,047 binding sites in rat liver.

The authors suggest that (+)-[3H]SKF 10,047 binding sites in liver and brain are a part of novel 'sigmergic' regulatory system.

The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate

The results suggest that reduction of synaptic excitation mediated via NMA receptors contributes to the anaesthetic/analgesic properties of these two dissociative anaesthetics.

Drugs acting on sigma and phencyclidine receptors: a review of their nature, function, and possible therapeutic importance.

General summary of the pharmacological properties of phencyclidine and related drugs and then to consider in more detail their actions at the cellular level. Phencyclidine and σ receptors