Biomedical subjects

P Seeman

Publications and source records attributed to P Seeman.

At least 271 records · Page 15Linked to original sources

PubMed1976

Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug.

In order to develop a better dopamine receptor radioligand, [3H[apomorphine was prepared and tested for dopamine-like binding properties in both calf and human brain tissues. Specific binding of [3H]apomorphine was defined as that binding which occurred in the presence of 1 muM (-)-butaclamol (an inactive neuroleptic) minus that occurring in the presence of 1 muM (+)-butaclamol (active neuroleptic). The specific binding was saturable, the number of sites being double that of specific [3H]dopamine binding, and occurred primarily in dopamine-rich regions of postmortem human brains. The binding had a dissociation constant of 0.9 nM for human caudate (2 nM for calf caudate) and was blocked by dopamine and norepinephrine, but not by isoproterenol or (-)-propranolol, distinguishing it from a beta-adrenergic receptor. Since there was little desorption of [3H]apomorphine, the ligand permits extensive washing during routine assays for dopamine receptors, and facilitates biochemical purification of the receptor.

Affinity Labels↗

PubMed1976

Catalepsy induced by morphine or haloperidol: effects of apomorphine and anticholinergic drugs.

To investigate the extent of cholinergic involvement in opiate-induced catalepsy, the effects of three anticholinergic drugs were studied on morphine-induced catalepsy. Haloperidol-induced catalepsy was also examined. Maximum catalepsy in rats was obtained with 30 mg/kg morphine or 3 mg/kg haloperidol. The anticholinergic drugs atropine, benztropine, and scopolamine were unable to antagonize morphine-induced catalepsy, yet readily antagonized haloperidol-induced catalepsy. Low doses of apomorphine (7.5 mg/kg), on the other hand, readily antagonized morphine catalepsy, but 13-fold higher doses of apomorphine were needed to block haloperidol-induced catalepsy. The results are compatible with the idea that catalepsy can be mediated via the striatum or the amygdala; morphine-dopamine antagonism may occur in the amygdala, whereas morphine-dopamine-cholinergic interactions occur in the striatum.

Animals↗

PubMed1976

Dopamine/neuroleptic receptors in basal hypothalamus and pituitary.

In order to determine whether the basal hypothalamus or the pituitary (or both) is the likely locus of action of the tuberoinfundibular (TI) dopamine neurons, these regions were examined for dopamine and neuroleptic receptors. High affinity receptors for haloperidol and dopamine were found in the rat pituitary while none were detected in rat basal hypothalamus. The relative ability of two neuroleptics, chlorpromazine and haloperidol, to displace (3H)haloperidol from the receptor in monkey pituitary is similar to that for rat striatum. The lack of receptors capable of binding (3H)haloperidol or (3H)dopamine in the basal hypothalamus strongly suggests that the TI neurons do not produce postsynaptic effects in this region. The pituitary receptors for (3H)haloperidol and (3H)dopamine have the characteristics of a functional system. The presence of neuroleptic/dopamine receptors in the pituitary and lack of such receptors in the basal hypothalamus supports the hypothesis that dopamine may act directly as a prolactin release inhibiting factor (PIF) rather than releasing PIF from adjacent nerve terminals in the median eminence.

Animals↗

PubMed1975

Letter: cH OR PH.

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Education, Medical, Undergraduate↗

PubMed1975

Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons.

Neuroleptic (antipsychotic) drugs inhibited the electrically stimulated release of [3-H] dopamine from rat striatal slices. The concentrations for 50 percent inhibition (ranging from 11.5 nanomolar for spiroperidol to 800 nanomolar for thioridazine) correlated closely with the average daily dosages of 25 neuroleptic drugs used clinically for schizophrenia. The correlation includes butyrophenones, phenothiazines, reserpine, pimozide, clozapine, and (plus)- butaclamol. Clinically inactive isomers [trans-thiothixene, trans-flupenthixol, and (minus)-butaclamol] required 20 to 1000 times higher concentrations than the active isomers to inhibit release. Compared to the inhibition of [3-H] dopamine release, much higher neuroleptic concentrations were needed to inhibit the electrically stimulated release of other neurotransmitters--[3-H] acetylcholine, [3-H-a1 (gamma-aminobutyric acid). The neuroleptic drugs may block the presynaptic coupling between impulse and neurosecretion.

Acetylcholine↗

PubMed1975

Brain receptors for antipsychotic drugs and dopamine: direct binding assays.

In order to test the suggestion that antipsychotic drugs act by blocking dopamine receptors in the brain, the direct effects of such neuroleptic drugs were tested on the stereospecific binding of [3H]dopamine and of [3H]haloperidol to rat brain striata and their subfractions. The stereospecific component of binding was defined as that amount of [3h]dopamine or [3H]haloperidol bound in the presence of (-)-butaclamol (an inactive drug) minus that bound in the presence of (+)-butaclamol (a potent neuroleptic drug); 100 nM butaclamol was used for the [3H]haloperidol assay, while 1 muM butaclamol was used for the [3H]dopamine assay. Various antipsychotic drugs inhibited this stereospecific component in both the dopamine and haloperidol assays. These inhibitory potencies correlated with the clinical doses used for controlling schizophrenia.

Animals↗

PubMed1975

Different sites of membrane action for tetrodotoxin and lipid-soluble anesthetics.

1. To examine whether different local anesthetics act on different or similar sites in the nerve membrane, the effects of combinations of lipid-soluble anesthetics and tetrodotoxin (TTX) were studied on the compound action potential of the frog sciatic nerve. 2. The nerve-blocking potency of TTX was potentiated 5-fold by benzyl alcohol and 10-fold by lidocaine, at concentrations of these latter two drugs which were just barely anesthetic; no such synergism occurred between saxitoxin (STX) and TTX, their combined effect being merely additive. 3. Simple additive effects also occurred between benzyl alcohol and phenol, benzyl alcohol and urethane, as well as lidocaine with a spirosuccinimide, RAC 109 II. 4. Synergism occurred between STX and 2-aminobenzimidazole. 5. A small but consistent synergism occurred between lidocaine and benzyl alcohol. 6. It is concluded that uncharged anesthetics, tertiary amines, and TTX act via different membrane binding sites which are all closely associated with the Na+ conductance channels.

Action Potentials↗

PubMed1974