Abstract
The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-[3H]SKF 10,047 (N-allylnormetazocine) and to dopamine D2 sites was investigated. In guinea pig brain membranes, (+)-[3H]SKF 10,047 bound to a single class of sites with a Kd of 4 X 10(-8) M and a Bmax of 333 fmol/mg of protein. This binding was different from mu, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[3H]SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol greater than perphenazine greater than fluphenazine greater than acetophenazine greater than trifluoperazine greater than molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-[3H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[3H]SKF 10,047 binding sites did not correlate with those for [3H]spiperone (dopamine D2) sites. [3H]-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-SKF 10,047. In the striatum, about half of the saturable [3H]haloperidol binding was to [3H]spiperone (D2) sites and the other half was to sites similar to (+)-[3H]SKF 10,047 binding sites.
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- Aceto M. D., May E. L. Antinociceptive studies of the optical isomers of N-allylnormetazocine (SKF 10,047). Eur J Pharmacol. 1983 Jul 22;91(2-3):267–272. doi: 10.1016/0014-2999(83)90476-4. [DOI] [PubMed] [Google Scholar]
- De Wied D., Kovács G. L., Bohus B., Van Ree J. M., Greven H. M. Neuroleptic activity of the neuropeptide beta-LPH62-77 ([Des-Tyr1]gamma-endorphin; DT gamma E). Eur J Pharmacol. 1978 Jun 15;49(4):427–436. doi: 10.1016/0014-2999(78)90317-5. [DOI] [PubMed] [Google Scholar]
- Haertzen C. A. Subjective effects of narcotic antagonists cyclazocine and nalorphine on the Addiction Research Center Inventory (ARCI). Psychopharmacologia. 1970;18(4):366–377. doi: 10.1007/BF00402763. [DOI] [PubMed] [Google Scholar]
- List S. J., Seeman P. Resolution of dopamine and serotonin receptor components of [3H]spiperone binding to rat brain regions. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2620–2624. doi: 10.1073/pnas.78.4.2620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lord J. A., Waterfield A. A., Hughes J., Kosterlitz H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977 Jun 9;267(5611):495–499. doi: 10.1038/267495a0. [DOI] [PubMed] [Google Scholar]
- Martin W. R., Eades C. G., Thompson J. A., Huppler R. E., Gilbert P. E. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976 Jun;197(3):517–532. [PubMed] [Google Scholar]
- Seeman P. Brain dopamine receptors. Pharmacol Rev. 1980 Sep;32(3):229–313. [PubMed] [Google Scholar]
- Su T. P. Evidence for sigma opioid receptor: binding of [3H]SKF-10047 to etorphine-inaccessible sites in guinea-pig brain. J Pharmacol Exp Ther. 1982 Nov;223(2):284–290. [PubMed] [Google Scholar]
- Tam S. W. Naloxone-inaccessible sigma receptor in rat central nervous system. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6703–6707. doi: 10.1073/pnas.80.21.6703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vaupel D. B. Naltrexone fails to antagonize the sigma effects of PCP and SKF 10,047 in the dog. Eur J Pharmacol. 1983 Sep 2;92(3-4):269–274. doi: 10.1016/0014-2999(83)90297-2. [DOI] [PubMed] [Google Scholar]
- Zukin R. S., Zukin S. R. Demonstration of [3H]cyclazocine binding to multiple opiate receptor sites. Mol Pharmacol. 1981 Sep;20(2):246–254. [PubMed] [Google Scholar]