Neuroleptic receptors: Stereoselectivity for neuroleptic enantiomers

Seeman, Philip; Westman, Karen; Protiva, M.; Jílek, J. O.; Jain, P. C.; Saxena, Anil Kumar; Anand, N.; Humber, Leslie G.; Philipp, Adolf

doi:10.1016/0014-2999(79)90177-8

Cited by 36 publications

(15 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1), is a dopamine receptor blocker [Seeman et al" 1979], Its pharmacological profile resembles that of haloperidol. Centbutindole, however, does not produce hypothermia and has a greater separation between doses causing catalepsy and neurolepsy [Dua et ai., 1974;Anand, 1983], The dose of haloperidol was based on studies of Vogelsang and Piercy [1985], Centbutindole blocks the conditioned avoid ance response and produces catalepsy at half * p < 0.05 as compared to control (vehicle) group.…”

Section: Discussionmentioning

confidence: 99%

Effect of Melanotropin Release Inhibiting Factor on Changes by Haloperidol and Centbutindole in Cerebral Cortical 5-Hydroxytryptamine Receptors

Gulati¹,

Bhargava²

1990

Pharmacology

View full text Add to dashboard Cite

The effect of melanotropin release inhibiting factor (Pro-Leu-Gly-NH₂, MIF) was determined on changes induced by two neuroleptics, haloperidol and centbutindole, in cerebral cortical 5-hydroxytryptamine (5-HT) receptors. Male Sprague-Dawley rats were injected daily i.p. with vehicle, haloperidol (1.0 mg/kg) or centbutindole (0.5 mg/kg), respectively, for 21 days. On day 22, these 3 groups were further divided into 2 subgroups and injected with either vehicle or MIF (2.0 mg/kg, i.p.) daily for 3 days. ³H-5-HT was used to study 5-HT₁ receptors, and ³H-spiroperidol to label 5-HT₂ receptors in the cerebral cortex. Chronic administration of haloperidol significantly increased (39.7%) the maximal binding capacity (B_max) of ³H-5-HT binding to 5-HTj receptors. Dissociation constant (K_d) values did not change. Centbutindole had no effect on 5-HTι receptors. MIF had no effect on 5-HT₁ receptors, nor did it alter haloperidol-induced increases in the B_max of ³H-5-HT binding to 5-HT₁ receptors. Chronic administration of centbutindole significantly increased (61.1%) the B_max of ³H-spiroperidol binding to 5-HT₂ receptors. No change occurred in the IQ values. Chronic treatment with haloperidol had no effect on 5-HT₂ receptor characteristics. MIF had no effect on 5-HT₂ receptors or on the increase in 5-HT₂ receptor density induced by centbutindole. The behavioral syndrome induced by 5-hydroxytryptophan (5-HTP) (50, 100 and 200 mg/kg, i.p.) was also measured in rats treated chronically with haloperidol or centbutindole. Haloperidol had no effect on the 5-HTP syndrome, whereas centbutindole stimulated by 24–45% the intensity of the syndrome. MIF had no effect on the 5-HTP syndrome, nor did it alter the increase induced by centbutindole. It is concluded that haloperidol and centubutindole differentially affect cortical 5-HT₁ and 5-HT₂ receptors. MIF does not by itself affect 5-HT receptors, nor does it reverse the up-regulation of 5-HT receptors induced by haloperidol and centbutindole.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of Melanotropin Release Inhibiting Factor on Changes by Haloperidol and Centbutindole in Cerebral Cortical 5-Hydroxytryptamine Receptors

Gulati¹,

Bhargava²

1990

Pharmacology

View full text Add to dashboard Cite

show abstract

“…It has been proposed that several psychiatric illnesses are caused by hyperdopaminergic activity in dopaminergic pathways. The hypothesis that the dopaminergic system is overactive in schizophrenia is based on the finding of a correlation between the potency of neuroleptics as dopamine antagonists and their clinically effective doses [4]. Therefore, in an effort to gain a greater understanding of the D 2 GPCR and the residues involved in the conformational rearrangement within the transmembrane region, a number of theoretical models were constructed.…”

Section: Introductionmentioning

confidence: 99%

Analysis of agonism by dopamine at the dopaminergic D 2 G-protein coupled receptor based on comparative modelling of rhodopsin

Tehan¹,

Lloyd²,

Wong³

et al. 2002

Molecular Simulation

View full text Add to dashboard Cite

A number of theoretical dopaminergic D 2 models were constructed using comparative modelling techniques. The models constructed were based on the recently published crystal structure of rhodopsin. D 2 models were constructed without any ligands bound in the active site and also with the endogenous agonist, dopamine, bound in the active site. Comparison of the bound and unbound models revealed the importance of the chi angle of serine 197 and the effect this has on the bending of helix 5 when an agonist is present in the binding site.

show abstract

“…selectively inhibited by the (d)-enantiomer of butaclamol (Seeman et al, 1979) and agonist binding to DA receptors is regulated by guanine nucleotide Creese et al, , 1979Zahniser and Molinoff, 1978) and sodium chloride (Usdin et al, 1980). To gain information on the biochemical properties and the ontogenetic development of DA receptors, we investigated the effects of Na+, GTP, and several DA receptor agonists and antagonists on [3H]spiperone binding to striatal membranes of developing rats.…”

mentioning

confidence: 99%

Ontogenetic Development of the Striatal [³H]Spiperone Binding: Regulation by Sodium and Guanine Nucleotide in Rats

Nomura

Oki

Segawa

1982

Journal of Neurochemistry

View full text Add to dashboard Cite

Ontogenetic development of specific [3H]spiperone binding to crude synaptic membranes and its regulation by Na+ and GTP was investigated in the rat striatum. (d)-Butaclamol more effectively inhibited [3H]spiperone binding than (l)-butaclamol. The ratio of inhibitory activity of (d)- and (l)-butaclamol for [3H]spiperone binding was not different between 1-, 7-, and 70-day-old animals but eight- to ninefold lower at 18 days of gestation than during the postnatal period. A Scatchard plot of specific binding indicated the presence of two types of binding: low-affinity (KD = 1.51 nM) and high-affinity (KD = 0.09 nM) binding on day 70. Only one component (KD = 0.075 nM) was observed on days 1 and 7 and both types of binding were found on day 15. Bmax gradually increased with age and reached a peak on day 30, followed by a decline on days 70 and 360. Na+, 100 mM, significantly increased specific binding on days 1, 7, 15, and 70. GTP, 50 microM, completely reversed the Na+-induced decrease in IC50 of apomorphine on both days 15 and 70, but not on day 7. It is suggested that receptors could recognize ligand stereospecificity on day 1. The density in dopamine receptors in the striatum reaches a peak on day 30, followed by a decrease on days 70 and 360. In addition, regulation by Na+ and GTP in agonist binding to dopamine receptors seems to become functional between 1 and 2 weeks after birth.

show abstract

Neuroleptic receptors: Stereoselectivity for neuroleptic enantiomers

Cited by 36 publications

References 9 publications

Effect of Melanotropin Release Inhibiting Factor on Changes by Haloperidol and Centbutindole in Cerebral Cortical 5-Hydroxytryptamine Receptors

Effect of Melanotropin Release Inhibiting Factor on Changes by Haloperidol and Centbutindole in Cerebral Cortical 5-Hydroxytryptamine Receptors

Analysis of agonism by dopamine at the dopaminergic D 2 G-protein coupled receptor based on comparative modelling of rhodopsin

Ontogenetic Development of the Striatal [³H]Spiperone Binding: Regulation by Sodium and Guanine Nucleotide in Rats

Contact Info

Product

Resources

About

Neuroleptic receptors: Stereoselectivity for neuroleptic enantiomers

Cited by 36 publications

References 9 publications

Effect of Melanotropin Release Inhibiting Factor on Changes by Haloperidol and Centbutindole in Cerebral Cortical 5-Hydroxytryptamine Receptors

Effect of Melanotropin Release Inhibiting Factor on Changes by Haloperidol and Centbutindole in Cerebral Cortical 5-Hydroxytryptamine Receptors

Analysis of agonism by dopamine at the dopaminergic D 2 G-protein coupled receptor based on comparative modelling of rhodopsin

Ontogenetic Development of the Striatal [3H]Spiperone Binding: Regulation by Sodium and Guanine Nucleotide in Rats

Contact Info

Product

Resources

About

Ontogenetic Development of the Striatal [³H]Spiperone Binding: Regulation by Sodium and Guanine Nucleotide in Rats