The effects of standard neuroleptic compounds on the binding of 3H-spiroperidol in the striatum and mesolimbic system of the rat in vitro

Howard, Joy L.; Large, Bruce T.; Wedley, Susan; Pullar, Ian A.

doi:10.1016/0024-3205(78)90039-5

Cited by 30 publications

(4 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Evidence from receptor binding (Howard et al 1978;Altar et al 1986), behavioural pharmacology MacDonald 1984, 1985;Ljungberg and Ungerstedt 1985), electrophysiology (White and Wang 1983;Chiodo and Bunney 1985), and in vivo electrochemistry Lane and Blaha 1987) indicate that atypical neuroleptics may act preferentially at sites in the mesolimbic DA system, including the nucleus accumbens, whereas metoclopramide may have a selective action on DA function in the striatum.…”

Section: Discussionmentioning

confidence: 95%

Blockade of acquisition of one-way conditioned avoidance responding by haloperidol and metoclopramide but not by thioridazine or clozapine: implications for screening new antipsychotic drugs

Blackburn

Phillips

1989

Psychopharmacology

View full text Add to dashboard Cite

The classical neuroleptic drugs haloperidol and pimozide have a strong disruptive effect on the acquisition of conditioned avoidance responding (CAR), yet have relatively little impact on the performance of previously acquired responses. Separate experiments compared the effects of haloperidol, two atypical neuroleptics, thioridazine and clozapine, and a substituted benzamide, metoclopramide, on one-way avoidance by rats. Thioridazine (10-50 mg/kg) and clozapine (1.25-10.0 mg/kg) disrupted both acquisition and performance of CAR. In contrast, haloperidol (0.075-0.150 mg/kg) and metoclopramide (5.0-7.5 mg/kg) completely blocked the acquisition of CAR, yet initially produced only a slight disruption in the performance of a previously acquired response. The ineffectiveness of the atypical neuroleptics in producing a complete disruption of acquisition of CAR may be due to the anticholinergic properties of these drugs. Alternatively, the differences between metoclopramide and the atypical neuroleptics may be due to a preferential effect of metoclopramide on striatal or amygdaloid dopamine neurotransmission. These results suggest that caution should be exercised in using CAR as an animal model for assessing the antipsychotic potential of new pharmacological agents.

show abstract

Section: Discussionmentioning

confidence: 95%

Blockade of acquisition of one-way conditioned avoidance responding by haloperidol and metoclopramide but not by thioridazine or clozapine: implications for screening new antipsychotic drugs

Blackburn

Phillips

1989

Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…Although the neuropharmacology of metoclopramide has been little studied during the past 2 decades, early studies reported that, by contrast with other neuroleptics, metoclopramide is inactive as an antagonist of dopamine-stimulated adenylate cyclase (Roufogalis et al 1976) and as a competitive inhibitor of spiroperidol binding (Howard et al 1978), leading to the suggestion that metoclopramide "may be binding to a specific and different receptor subpopulation" (Peselow and Stanley 1982, p. 178). The relative affinity of metoclopramide for D 1 , D 2 , D 3 , D 4 , or even D 5 dopamine receptors is unknown.…”

Section: Discussionmentioning

confidence: 96%

Use of the "Inverse Neuroleptic" Metoclopramide in Tourette Syndrome: An Open Case Series

Acosta

2004

Journal of Child and Adolescent Psychopharmacology

View full text Add to dashboard Cite

Neuroleptics are generally highly effective in suppressing tics, but their many adverse effects limit their usefulness. Animal studies have shown that, compared with both typical and atypical neuroleptics, metoclopramide has effects that are regionally circumscribed to rat motor striatum. Based on this observation and two prior case reports, metoclopramide was openly prescribed and individually titrated to diminish tics in 10 patients with Tourette syndrome. All patients improved on the Yale Global Tic Severity Scale by an average of 55%. Although we did not observe frank extrapyramidal symptoms, including tardive dyskinesia, these data are not sufficient to support clinical recommendations because of many limitations, including the absence of systematic ratings of nontic abnormal movements. However, controlled clinical studies and additional basic investigations of metoclopramide are warranted.

show abstract

“…Initial results from in vitro and ex vivo radioligand binding studies, using "H-haloperidol and 3H-spiperone, suggested that CLOZ may have a differential affinity for DA receptors in mesolimbic brain areas compared to extrapyramidal areas (Borison and Diamond, 1983;Howard et al, 1978;Kohler et al, 1981;Le Fur et al, 1979). A recent study has also shown that CLOZ is significantly more potent in inhibiting 3H-spiroperidol binding in the rat cortex compared to the striatum (Svartengren and Celander, 1994).…”

Section: Biochemical Studiesmentioning

confidence: 94%

Pharmacological actions of the atypical antipsychotic drug clozapine: A review

Ashby

Wang

1996

Synapse

167

View full text Add to dashboard Cite

Clozapine [8-chloro- 11-(4-methyl- 1-piperazinyl)-3H-dibenzo (b,e)(1,4) diazepine], or clozaril, is a member of the dibenazepine class of antipsychotic drugs. Initially, studies in animals using a number of neurochemical, biochemical, electrophysiological, and behavioral paradigms indicated that clozapine was markedly different from various typical antipsychotic drugs such as haloperidol and chlorpromazine. Subsequently, clinical studies have shown that clozapine is effective in ameliorating the core symptoms, as well as the negative symptoms, in schizophrenia. However, clozapine has a much lower propensity for inducing neurological side effects after acute or repeated administration compared to various typical neuroleptics. Furthermore, clozapine is therapeutically effective in treating about 30% of schizophrenic patients who are resistant to standard antipsychotic drugs. Based on the above information, clozapine has been designated an atypical antipsychotic drug. However, at this time, it is not entirely clear why clozapine is such a unique antipsychotic drug. To date, there has not been a comprehensive review regarding clozapine's pharmacological profile. Therefore, we will review clozapine's profile in the following areas: 1) affinity for neurotransmitter receptors in the brain; 2) electrophysiology (in vivo, single-cell recording and iontophoresis; in vitro studies); 3) in vivo microdialysis and voltammetry; 4) monoamine turnover or metabolism; 5) intermediate early gene expression; 6) positron emission tomography studies; and 7) molecular biological studies. We will also compare and contrast clozapine's acute and chronic effects, and discuss the merits of various hypotheses that have been put forward to explain clozapine's unique profile.

show abstract

The effects of standard neuroleptic compounds on the binding of 3H-spiroperidol in the striatum and mesolimbic system of the rat in vitro

Cited by 30 publications

References 15 publications

Blockade of acquisition of one-way conditioned avoidance responding by haloperidol and metoclopramide but not by thioridazine or clozapine: implications for screening new antipsychotic drugs

Blockade of acquisition of one-way conditioned avoidance responding by haloperidol and metoclopramide but not by thioridazine or clozapine: implications for screening new antipsychotic drugs

Use of the "Inverse Neuroleptic" Metoclopramide in Tourette Syndrome: An Open Case Series

Pharmacological actions of the atypical antipsychotic drug clozapine: A review

Contact Info

Product

Resources

About