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Biomedical subjects

P Seeman

Publications and source records attributed to P Seeman.

At least 217 records · Page 12Linked to original sources
PubMed1981

Tardive dyskinesia in schizophrenic outpatients: prevalence and significant variables.

All the patients (N = 94) of an outpatient clinic for schizophrenia were evaluated for the presence and severity of neuroleptic induced tardive dyskinesia. Fourty-four percent of the patients showed some degree of tardive dyskinesia. The proportion of patients with tardive dyskinesia increased directly with age and with number of years of neuroleptic treatment. Recent dose reduction exacerbated the syndrome. There were no gender differences in the clinic as a whole. Severity of dyskinesia correlated with anticholinergic drug use, with the piperazine/butyrophenone group of neuroleptics and with the use of depot-administered drugs. The depot correlation was highly significant in the under-30 age group.

Administration, Oral↗
PubMed1980

Presynaptically acting catecholamines bind to alpha 2-adrenoceptors labelled by 3H-clonidine.

It is known that certain catecholamine congeners can decelerate the heart rate by inhibiting the prejunctional sympathetic neurones to the atrium. The present study was done to determine whether this presynaptic action might be associated with either dopamine receptors or alpha-adrenergic receptors. The effects of 10 catecholamine congeners wee tested on the specific binding of 0.2 nM 3H-WB-4101 and 0.2 nM 3H-clonidine to calf frontal cortex homogenates, and that of 2 nM 3H-apomorphine to calf caudate nucleus homogenates. The drugs tested were apomorphine, the aminotetralin M-7, 3 dialkylated dopamine congeners, and 5 congeners of octahydrobenzo(f)-quinoline. The IC50 values (concentrations for 50% inhibition of binding) ranged from 400 to 28,000 nM for 3H-WB-4101, from 3 to 270 nM for 3H-apomorphine, and from 9 to 1000 nM for 3H-clonidine. Only the IC50 values for 3H-clonidine binding correlated with the in vitro IC50 values for inhibiting atrial acceleration (data from Long et al., 1975, 1979). These findings suggest that 3H-clonidine appears to bind to the same site in brain (alpha 2-adrenoceptor) on which catecholaminergic drugs act to produce cardiodeceleration.

Animals↗
PubMed1980

Serotonin receptors in hippocampus and frontal cortex.

The inhibition by various serotonin agonists and antagonists of the binding of 3 nM 3H-d-LSD, 1.7 nM 3H-serotonin and 0.22 nM 3H-spiperone to homogenates of calf hippocampus and frontal cortex was studied. The 50% inhibitory concentration (IC50) for these drugs versus 3H-d-LSD binding had similar values to and correlated with corresponding IC50 values versus 3H-serotonin binding in the hippocampus, suggesting that 3H-LSD and 3H-serotonin label similar sites in this region. In the calf frontal cortex, serotonin revealed a biphasic inhibition against 3H-d-LSD binding and the tryptamines inhibited over a concentration range of 10 000-fold. The IC25 values of various drugs versus 3H-d-LSD binding correlated with the IC50 values versus 3H-serotonin, but did not correlate with the IC50 values versus 3H-spiperone. These data suggest that 3H-d-LSD bound to more than one serotonin site in the calf frontal cortex and that 3H-spiperone bound to a separate serotonergic site. Scatchard analyses of the binding for these three 3H-ligands indicated that in the calf frontal cortex the density of 3H-d-LSD sites was approximately equal to the sum of the densities for 3H-serotonin (S-1 sites) and 3H-spiperone (S-2 sites). Two weeks after serotonin-depleting radiofrequency heat lesions of the midbrain dorsal and median raphe nuclei in rats, both 3H-serotonin and 3H-LSD showed enhanced binding in the hippocampus. These data support previous suggestions that supersensitivity develops specifically in serotonin receptors following afferent denervation.

Animals↗
PubMed1980

The effects of long-term ethanol on brain receptors for dopamine, acetylcholine, serotonin and noradrenaline.

Rats were treated with ethanol for 11-15 days, after which the brain neurotransmitter receptors for dopamine, acetylcholine, serotonin and noradrenaline were measured. The rats were intubated at 12 h intervals with 4 g/kg ethanol, and sacrificed 10 h after the last intubation. After ethanol treatment, the specific binding of 3H-haloperidol to dopamine receptors was significantly decreased in the mesolimbic areas by 20 +/- 6%, but was unchanged in the striatum. Specific binding of 3H-serotonin was increased by 63 +/- 29% in the striatum and by 32 +/- 9% in the brainstem, but decreased by 20 +/- 7% in the hippocampus. The specific binding of 3H-quinuclidinyl benzilate to muscarinic acetylcholine receptors increased by 7 +/- 2% in the striatum, but decreased by 5 +/- 2% in the cerebral cortex. The specific binding of 3H-WB-4101 to alpha-adrenergic receptors was unchanged in all brain areas assayed, namely the striatum, mesolimbic areas, hippocampus, hypothalamus, brainstem and cerebral cortex. These changes may be related to some aspects of tolerance to, and dependence on, ethanol.

Adenylyl Cyclases↗
PubMed1980

Elevation of brain neuroleptic/dopamine receptors in schizophrenia.

To test the dopamine hypothesis of schizophrenia the authors measured specific 3H-neuroleptic/dopamine binding sites in three dopamin-rich regions of 59 postmortem normal human brains and 50 postmortem brains from schizophrenic patients using 3H-haloperidol and 3H-spiperone. The binding of 2 nM 3H-haloperidol and of 1 nM 3H-spiperone was significantly elevated in the brains from schizophrenic patients. The brain regions from patients who had no history of being treated with neuroleptic drugs also exhibited significantly higher binding of the 3H-neuroleptics. These results are compatible with the hypothesis that schizophrenia may be associated with an overactivity of postsynaptic dopamine receptors.

Adolescent↗
PubMed1980

Abnormal neuroleptic/dopamine receptors in schizophrenia.

In order to test the dopamine hypothesis of schizophrenia, the neuroleptic/dopamine receptors in three dopamine-rich regions of 53 postmortem normal human brains and 42 schizophrenic brains were measured using 3H-haloperidol and 3H-spiperone. The binding of 2 nM 3H-haloperidol was significantly elevated in the caudate nucleus (90 +/- 10%) and the putamen (61 +/- 6%) from schizophrenic brains. The binding of 1 nM 3H-spiperone was also elevated by 50 +/- 7% in schizophrenic caudate and 47 +/- 8% in the putamen. The nucleus accumbens from schizophrenic brains revealed an enhanced binding of 110 to 115%. In those schizophrenic patients who had no history of being treated with neuroleptic drugs the brain regions also exhibited significantly higher (29-80%) binding of 3H-neuroleptics. The results are compatible with the hypothesis that schizophrenia may be associated with an overactivity of postsynaptic dopamine receptors.

Adult↗
PubMed1979

Neuroleptic receptors: stereoselectivity for neuroleptic enantiomers.

In order to identify a pair of neuroleptic enantiomers with the highest stereoselective interaction with neuroleptic/dopamine receptors, the effects of eight pairs of neuroleptic enantiomers were tested on the specific binding of 3H-spiperone to crude homogenates of calf caudate nucleus. The ratios of the Ki values were: (+)-butaclamol/(-)-butaclamol = 3000; dexclamol/(-)-analogue = 151; (+)-isobutaclamol/(-)-isobutaclamol = 146; (-)-CTC/(+)-CTC= 109; (-)-centbutindole/(+)-centbutindole = 20; S(+)-octoclothepin/R(-)-octoclothepin = 11. Thus, the neuroleptic receptor is highly stereoselective for the rigid butaclamol derivatives, but much less so for the flexible neuroleptics. The 3H-apomorphine binding site, however, had a stereoselectivity ratio of only 7 for isobutaclamol, further suggesting that the high affinity sites (i.e. nM) for 3H-neuroleptic binding and for 3H-apomorphine binding are different.

Animals↗
PubMed1979

Selective labeling of apomorphine receptors by 3H-LSD.

There are at least two types of dopamine receptors: the 3H-dopamine or 3H-apomorphine receptor (with high or nM affinity for dopamine), and the 3H-neuroleptic receptor (with low or microM affinity for dopamine). While 3H-LSD can label the 3H-neuroleptic receptor, this study was done in order to label the 3H-apomorphine/dopamine receptor site. In the presence of excess phentolamine, serotonin and spiperone (to preclude binding to alpha-adrenergic, serotonergic and neuroleptic receptors, respectively) similar concentrations of dopaminergic drugs inhibited the binding (to calf caudate) of 3H-LSD and 3H-apomorphine. This is compatible with the concept that the 3H-apomorphine/dopamine receptor and the 3H-neuroleptic/dopamine receptor are separate.

Animals↗