Behavioral and biochemical stereoselectivity of sigma opiate/PCP receptors

Zukin, Stephen R.; Brady, Kathleen T.; Slifer, Barbara L.; Balster, Robert L.

doi:10.1016/0006-8993(84)91326-x

Cited by 100 publications

(51 citation statements)

References 10 publications

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“…Unlike the results obtained with dioxadrol or NANM, the ability of (+) and (-)cyclazocine to produce PCP-like behavioural effects or to displace bound q-LIOANDS AND DEXOXADROL BLOCK K+ CHANNELS [3H]PCP favours the laevorotatory enantiomorph since (-)cyclazocine is 2-to 8-fold more potent than (+)cyclazocine (Shannon, 1982b;Murray & Leid, 1984;Zukin, Brady, Slifer & Balster, 1984;Leander, Wood, Zimmerman & Dykstra, 1986). We have found (Fig.…”

Section: Effects Of the O-ligand Cyclazocinecontrasting

confidence: 44%

Psychotomimetic sigma‐ligands, dexoxadrol and phencyclidine block the same presynaptic potassium channel in rat brain.

Bartschat

Blaustein

1988

The Journal of Physiology

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Section: Effects Of the O-ligand Cyclazocinecontrasting

confidence: 44%

Psychotomimetic sigma‐ligands, dexoxadrol and phencyclidine block the same presynaptic potassium channel in rat brain.

Bartschat

Blaustein

1988

The Journal of Physiology

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“…These effects were initially postulated to reflect activation of brain 'a' receptors (Shannon, 1982;Zukin et al, 1984). However, recent radioligand binding studies using the prototypical a ligand, [3H]-( + )-NANM, have demonstrated that (+ )-NANM labels two distinct recognition sites in cerebral membranes: a high affinity site sensitive to nanomolar concentrations of haloperidol and a lower affinity site which corresponds to the recognition site labelled by [3H]-PCP (Zukin & Zukin, 1979;Vincent et al, 1979;Su, 1982;Tam, 1983;Largent et al, 1984;Martin et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Evidence against an involvement of the haloperidol‐sensitive σ recognition site in the discriminative stimulus properties of (+)‐N‐allylnormetazocine ((+)‐SKF 10,047)

Singh¹,

Wong²,

Kesingland³

et al. 1990

British J Pharmacology

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1 The involvement of the haloperidol-sensitive, a recognition site and the N-methyl-D-aspartic acid (NMDA) receptor in the mediation of the discriminative stimulus properties of (+)-N-allylnormetazocine ((+)-NANM, (+)-SKF 10,047), has been investigated in the rat by use of a two-lever, operant drug discrimination paradigm.2 Six compounds with nanamolar affinity for the a recognition site ((±)-pentazocine, (+)-3-(hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), ditolylguanidine (DTG), haloperidol, (-)-butaclamol and BMY 14802) were investigated for their ability to generalise or antagonise the (+)-NANM discriminative stimulus. Each drug was tested at doses found in an ex vivo radioligand binding assay to displace [3H]-DTG from the central a recognition site by more than 40%. 3 While (±)-pentazocine (in the presence of naloxone) generalised and (+)-3-PPP partially antagonised the (+)-NANM cue, the other putative a ligands were ineffective either as agonists or antagonists at doses clearly occupying the a site in vivo. 4 Dose-dependent generalisation to the (+)-NANM cue was seen with the selective non-competitive NMDA receptor antagonist, MK-801, a compound devoid of significant affinity for the a recognition site. 5 (±)-Pentazocine was found to antagonise seizures induced in the mouse by NMDLA, a model reflecting antagonism of central NMDA receptors, and a strong correlation was found between the rank order of potency of compounds to generalise to the (+)-NANM discriminative stimulus and their potencies as anticonvulsants. 6 In conclusion, no evidence was found to substantiate the contention that the discriminative stimulus properties of (+)-NANM are mediated by the haloperidol-sensitive a recognition site. On the other hand, the results are consistent with the interoceptive stimulus being mechanistically based in the NMDA receptor complex.

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“…Since (±)-SKF10,047 and cyclazocine have been found to bind to the PCP site, it has been suggested that the a effects of these opioids may be mediated through the PCP receptor (Zukin & Zukin, 1981). Furthermore, binding studies have shown that the (+ )-isomer displays selectivity for the a and PCP sites (Zukin et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

“…These observations have led to the proposition that both a opioids and PCP exert their behavioural effects via a common receptor mechanism (Zukin et al, 1984 have presented preliminary evidence (Downes et al, 1985) that in the rat brain the a and PCP sites are not the same, (+ )-[3H]-SKFIO,047, the selective a ligand, and [3H]-PCP, binding to more than one site. These findings agree well with those of Tam (1983Tam ( , 1985 in rat spinal cord and guinea-pig membranes.…”

Section: Introductionmentioning

confidence: 99%

A comparison of the binding of σ opioids and phencyclidine, and the interaction with antipsychotic drugs in rat brain membranes

Downes¹,

Lewis²,

Stone³

1986

British J Pharmacology

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Behavioral and biochemical stereoselectivity of sigma opiate/PCP receptors

Cited by 100 publications

References 10 publications

Psychotomimetic sigma‐ligands, dexoxadrol and phencyclidine block the same presynaptic potassium channel in rat brain.

Psychotomimetic sigma‐ligands, dexoxadrol and phencyclidine block the same presynaptic potassium channel in rat brain.

Evidence against an involvement of the haloperidol‐sensitive σ recognition site in the discriminative stimulus properties of (+)‐N‐allylnormetazocine ((+)‐SKF 10,047)

A comparison of the binding of σ opioids and phencyclidine, and the interaction with antipsychotic drugs in rat brain membranes

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