Psychotomimetic Opiate Receptors Labeled and Visualized with (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1984 Aug 1

PMID 6087359

Citations 39

Authors

B L Largent

A L Gundlach

S H Snyder

Affiliations

Soon will be listed here.

Abstract

3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP) has been proposed as a selective dopamine autoreceptor agonist in the central nervous system. This report describes the pharmacology and localization of specific high-affinity binding sites for (+)-[3H]3-PPP in brain. The drug specificity of (+)-[3H]3-PPP binding is identical to that of sigma receptors, which may mediate psychotomimetic effects of some opiates. Haloperidol and the opioid derivatives, pentazocine, cyclazocine, and SKF 10,047 are potent inhibitors of (+)-[3H]3-PPP binding. Stereoselectivity is exhibited for the (+) isomers of cyclazocine and SKF 10,047 at the sigma site, opposite to the stereoselectivity seen at mu, delta, and kappa opiate receptors. (+)-[3H]3-PPP does not label dopamine receptors, as potent dopamine agonists and antagonists are weak inhibitors of binding and the localization of specific (+)-[3H]3-PPP binding sites does not parallel that of dopamine neurons. Discrete localizations of (+)-[3H]3-PPP binding sites in many brain areas including limbic, midbrain, brainstem, and cerebellar regions may explain psychotomimetic actions of opiates and behavioral effects of 3-PPP.

Citing Articles

"Selective" serotonin 5-HT receptor antagonists.

Casey A, Cui M, Booth R, Canal C Biochem Pharmacol. 2022; 200:115028.

PMID: 35381208 PMC: 9252399. DOI: 10.1016/j.bcp.2022.115028.

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?.

Vela J Front Pharmacol. 2020; 11:582310.

PMID: 33364957 PMC: 7751758. DOI: 10.3389/fphar.2020.582310.

Sigma 1 receptor: A novel therapeutic target in retinal disease.

Smith S, Wang J, Cui X, Mysona B, Zhao J, Bollinger K Prog Retin Eye Res. 2018; 67:130-149.

PMID: 30075336 PMC: 6557374. DOI: 10.1016/j.preteyeres.2018.07.003.

The non-apoptotic action of Bcl-xL: regulating Ca(2+) signaling and bioenergetics at the ER-mitochondrion interface.

Williams A, Hayashi T, Wolozny D, Yin B, Su T, Betenbaugh M J Bioenerg Biomembr. 2016; 48(3):211-25.

PMID: 27155879 PMC: 6737942. DOI: 10.1007/s10863-016-9664-x.

Synthesis and pharmacological characterization of a novel sigma receptor ligand with improved metabolic stability and antagonistic effects against methamphetamine.

Seminerio M, Robson M, Abdelazeem A, Mesangeau C, Jamalapuram S, Avery B AAPS J. 2011; 14(1):43-51.

PMID: 22183188 PMC: 3291180. DOI: 10.1208/s12248-011-9311-8.

References

Brady K, Balster R, May E . Stereoisomers of N-allylnormetazocine: phencyclidine-like behavioral effects in squirrel monkeys and rats. Science. 1982; 215(4529):178-80. DOI: 10.1126/science.6274022. View

Strittmatter S, Lo M, Javitch J, Snyder S . Autoradiographic visualization of angiotensin-converting enzyme in rat brain with [3H]captopril: localization to a striatonigral pathway. Proc Natl Acad Sci U S A. 1984; 81(5):1599-603. PMC: 344885. DOI: 10.1073/pnas.81.5.1599. View

Hampton R, Medzihradsky F, Woods J, Dahlstrom P . Stereospecific binding of 3H-phencyclidine in brain membranes. Life Sci. 1982; 30(25):2147-54. DOI: 10.1016/0024-3205(82)90288-0. View

Unnerstall J, Niehoff D, Kuhar M, Palacios J . Quantitative receptor autoradiography using [3H]ultrofilm: application to multiple benzodiazepine receptors. J Neurosci Methods. 1982; 6(1-2):59-73. DOI: 10.1016/0165-0270(82)90016-4. View

Su T . Evidence for sigma opioid receptor: binding of [3H]SKF-10047 to etorphine-inaccessible sites in guinea-pig brain. J Pharmacol Exp Ther. 1982; 223(2):284-90. View

Haubrich D, Pflueger A . The autoreceptor control of dopamine synthesis. An in vitro and in vivo comparison of dopamine agonists. Mol Pharmacol. 1982; 21(1):114-20. View

Cheng Y, Prusoff W . Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 1973; 22(23):3099-108. DOI: 10.1016/0006-2952(73)90196-2. View

Martin W, EADES C, Thompson J, Huppler R, Gilbert P . The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976; 197(3):517-32. View

Pert C, Kuhar M, Snyder S . Opiate receptor: autoradiographic localization in rat brain. Proc Natl Acad Sci U S A. 1976; 73(10):3729-33. PMC: 431193. DOI: 10.1073/pnas.73.10.3729. View

10.

Zukin S, Zukin R . Specific [3H]phencyclidine binding in rat central nervous system. Proc Natl Acad Sci U S A. 1979; 76(10):5372-6. PMC: 413145. DOI: 10.1073/pnas.76.10.5372. View

11.

Vincent J, Kartalovski B, GENESTE P, Kamenka J, Lazdunski M . Interaction of phencyclidine ("angel dust") with a specific receptor in rat brain membranes. Proc Natl Acad Sci U S A. 1979; 76(9):4678-82. PMC: 411644. DOI: 10.1073/pnas.76.9.4678. View

12.

Roth R . Dopamine autoreceptors: pharmacology, function and comparison with post-synaptic dopamine receptors. Commun Psychopharmacol. 1979; 3(6):429-45. View

13.

Woolverton W, Martin B, Balster R . Modification of the behavioral effects of phencyclidine by repeated drug exposure and body weight changes. Pharmacol Biochem Behav. 1980; 12(5):761-6. DOI: 10.1016/0091-3057(80)90163-x. View

14.

Meibach R, Glicks D, Cox R, Maayani S . Localisation of phencyclidine-induced changes in brain energy metabolism. Nature. 1979; 282(5739):625-6. DOI: 10.1038/282625a0. View

15.

Goodman R, Snyder S, Kuhar M, Young 3rd W . Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography. Proc Natl Acad Sci U S A. 1980; 77(10):6239-43. PMC: 350251. DOI: 10.1073/pnas.77.10.6239. View

16.

Snyder S, Goodman R . Multiple neurotransmitter receptors. J Neurochem. 1980; 35(1):5-15. DOI: 10.1111/j.1471-4159.1980.tb12483.x. View

17.

Iwamoto E . Locomotor activity and antinociception after putative mu, kappa and sigma opioid receptor agonists in the rat: influence of dopaminergic agonists and antagonists. J Pharmacol Exp Ther. 1981; 217(2):451-60. View

18.

Hjorth S, Carlsson A, Wikstrom H, Lindberg P, Sanchez D, Hacksell U . 3-PPP, a new centrally acting DA-receptor agonist with selectivity for autoreceptors. Life Sci. 1981; 28(11):1225-38. DOI: 10.1016/0024-3205(81)90448-3. View

19.

Cowan A . Simple in vivo tests that differentiate prototype agonists at opiate receptors. Life Sci. 1981; 28(14):1559-70. DOI: 10.1016/0024-3205(81)90310-6. View

20.

Weiland G, Molinoff P . Quantitative analysis of drug-receptor interactions: I. Determination of kinetic and equilibrium properties. Life Sci. 1981; 29(4):313-30. DOI: 10.1016/0024-3205(81)90324-6. View