Search PubMed⌕ Search

Biomedical subjects

I Creese

Publications and source records attributed to I Creese.

At least 127 records · Page 7Linked to original sources
PubMed1978

3H-Haloperidol binding to dopamine receptors in rat corpus striatum: influence of chlorpromazine metabolites and derivatives.

A series of chlorpromazine metabolites and derivatives have been assayed for their ability to compete with 3H-haloperidol binding to dopamine receptors in membranes of rat corpus striatum. 3-Hydroxylation of chlorpromazine doubles affinity for receptor sites, while 7-hydroxychlorpromazine has a potency similar to that of chlorpromazine itself. Other patterns of hydroxylation reduce affinity. Side chain demethylation lowers affinity for binding sites. Several metabolites which lack neuroleptic activity in vivo, such as chlorpromazine-5-oxide, also are inactive in competing for 3H-haloperidol binding. Since blood levels of 7-hydroxychlorpromazine tend to be similar to those of chlorpromazine itself in patients, these observations indicate that 7-hydroxychlorpromazine may account for a major portion of the antischizophrenic efficacy of chlorpromazine. The structure--activity relationships observed in the present study support a model in which chlorpromazine interacts with dopamine receptors by assuming a conformation with its side chain tilted toward ring A.

Animals↗
PubMed1977

3H-Spiroperidol labels dopamine receptors in pituitary and brain.

3H-Spiroperidol of high specific radioactivity labels dopamine receptors in membranes of bovine caudate nucleus and anterior pituitary. The saturation and kinetic properties of 3H-spiroperidol binding are similar in the two tissues. In both caudate and pituitary 3H-spiroperidol displays very high affinity with a dissociation constant of 0.2-0.3 nM. The relative potencies of numerous dopamine agonists and antagonists in competing for 3H-spiroperidol binding are closely similar in anterior pituitary and caudate.

Animals↗
PubMed1977

Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity.

The binding of [3H]haloperidol to rat striatal dopamine receptors increases after lesion (made by injection of 6-hydroxydopamine) of the nigrostriatal dopamine pathway in those rats which are behaviorally supersensitive, as reflected by apomorphine-induced contralateral rotations. The enhanced binding is associated with an increased number of receptor sites with no change in their affinity.

Animals↗
PubMed1977

Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain.

Chronic treatment of rats with the neuroleptic drugs haloperidol, fluphenazine, and reserpine elicits a 20 to 25% increase in striatal dopamine receptor binding assayed with [3H]haloperidol. This increase in receptor sites may account for behavioral supersensitivity to dopamine receptor stimulants in such animals and for tardive dyskinesia in patients treated with these drugs.

Animals↗
PubMed1976

Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs.

Tritiated haloperidol and tritiated dopamine label postsynaptic dopamine receptors in mammalian brain. Clinical potencies of butyrophenones, phenothiazines, and related drugs correlate closely with their ability to inhibit tritiated haloperidol binding. These binding methods provide a simple in vitro means for evaluating new drugs as potential antischizophrenic agents.

Adenylyl Cyclases↗
PubMed1976

Butyrophenone influences on the opiate receptor.

Interaction of neuroleptic drugs with the opiate receptors was investigated by inhibition of the stereospecific binding of 3H-naloxone. Benperidol and pimozide, with IC50's of 0.3-0.5 muM, were more potent than the classical opiates meperidine and propoxyphene. A systematic structure-activity relationship was evident with the basic opiate structure of a benzene and a piperidine ring preserved in active compounds. No correlation between neuroleptic activity and binding to the opiate receptor was demonstrated.

Animals↗
PubMed1976

The opiate receptor: a model explaining structure-activity relationships of opiate agonists and antagonists.

A model of the opiate receptor is proposed which explains structure-activity relationships of opiate drugs, including (i) the unique potency of certain opiates such as etonitazene, fentanyl, phenazocine, and oripavines; (ii) the role of N-allyl substituents in conferring antagonist properties; and (iii) chemical features that afford "pure" antagonists. The model indicates mlecular mechanisms for interconversion of the opiate receptor between respective states that bind agonists or antagonists with high affinity.

Allosteric Regulation↗