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Biomedical subjects

R L Weir

Publications and source records attributed to R L Weir.

8 recordsLinked to original sources
PubMed1984

Interaction of anticonvulsant drugs with adenosine receptors in the central nervous system.

The anticonvulsant carbamazepine inhibits binding of 1 nM [3H]N6-cyclohexyladenosine to rat cerebral and cerebellar A1 adenosine receptors with an IC50 value of about 50 microM. This concentration is well within that expected for therapeutic regimens. Other anticonvulsants such as phenobarbital, phenytoin, primidone, valproate sodium, and ethosuximide had little or no effect on binding, while theophylline and caffeine caused marked inhibition. Carbamazepine had no marked effect on cyclic AMP levels in guinea pig cerebral cortical or hippocampal slices, but was a weak inhibitor (IC50 about 200 microM) of 2-chloroadenosine-elicited accumulations of cyclic AMP via an A2 adenosine receptor in cortical slices. Carbamazepine is thus a somewhat selective ligand for A1 adenosine receptors in brain. The nature of its activity at those receptors is unclear, but its lack of central stimulant effects contrasts to the stimulant properties of A1 adenosine receptor antagonist such as caffeine and theophylline.

Adenosine↗
PubMed1983

Interaction between methylxanthines and the benzodiazepine receptor.

3H-Flunitrazepam (500 pM) was used to estimate the inhibitory effects of caffeine, theophylline, theobromine and 3-methylxanthine on binding to rat brain homogenates. Caffeine and theophylline showed a low affinity competitive type of inhibition in vitro, but no inhibition in vivo. Low concentrations of caffeine failed to show clear inhibitory capabilities against low concentrations of 3H-flunitrazepam. The results suggest that only the toxic central nervous system effects of methylxanthines are mediated via the benzodiazepine receptor.

Animals↗
PubMed1981

Spinocerebellar degeneration with parkinsonian features: a clinical and pathological report.

A 20-year-old patient had spinocerebellar degeneration and parkinsonian tremor that improved with L-dopa treatment. Postmortem examination revealed posterior column atrophy in the spinal cord and severe degeneration in the substantia nigra. Atrophic changes were noted in deep cerebellar nuclei and superior cerebellar peduncles. This study confirms the relationships between clinical parkinsonism, substantia nigra atrophy, and the therapeutic effect of L-dopa.

Adult↗
PubMed1981

Binding of antiparkinsonian ergot derivatives to the dopamine receptor.

The effects of bromocriptine, lisuride and apomorphine on specific binding of 3H-spiroperidol to homogenates of rat caudate nucleus were studied. (+)-Butaclamol was used to define specific binding. Bromocriptine and lisuride inhibited binding markedly, in vitro and also 30 min after in vivo injection. Bromocriptine continued to inhibit binding 24h after a single injection and also after 4 days of drug administration. Lisuride did not affect net specific binding at these periods. Apomorphine produced a mild reduction in binding after 30 min but none after 4 days. It appears that the ergot alkaloids inhibit binding of 3H-spiroperidol by binding strongly to the dopamine receptor.

Animals↗
PubMed1980

Extrapyramidal dysfunction in alcoholism.

Chronic, excessive ingestion of alcohol, with its accompanying subnutrition and intermittent drug withdrawal (partial or complete), has produced many neurologic disorders. These problems include involuntary movement disorders which may be reviewed under three major headings: withdrawal tremulous states, cerebellar system dysfunction, and hepatic related disorders.The tremor of alcohol withdrawal resembles that of physiologic tremor when exacerbated by anxiety. It is the most common neurologic manifestation of alcohol withdrawal, and the tremor amplitude is usually greatest some 10 to 20 hours after cessation of drinking. A tremulous state, which may be transient or persistent, also occurs in infants born to alcoholic mothers.The common hepatic encephalopathy may be accompanied by a flapping tremor and multiple other tremors and jerking movements. Chronic porto-systemic encephalopathy is accompanied by choreoathetoid movements and persistent coarse tremors.

Alcoholism↗
PubMed1978

Inhibition of fast axoplasmic transport by acrylamide.

The effect of acrylamide on fast axoplasmic transport in the cat sciatic nerve was studied in vivo and in vitro by the technique of isotope injection. [14C]leucine was injected into the lumbar dorsal root ganglia. In cats fed daily doses of acrylamide over 1 to 4 weeks, the rate of transport was 286 mm/day compared with 424 mm/day in controls. In vitro incubation of the sciatic nerve with acrylamide (2 x 10(-2) M and 2 x 10(-4) M) demonstrated no such inhibition. Study of the results and review of the literature suggest that acrylamide acted subacutely on metabolism of amino acid and protein in the nerve axon, probably in the smooth endoplasmic reticulum.

Acrylamides↗
PubMedDate not supplied

Inhibition of N6-[3H]cyclohexyladenosine binding by carbamazepine.

The mechanism of action of carbamazepine (CBZ) (Tegretol), despite widespread use in the management of partial and tonic-clonic seizures in adults, is not completely understood. In animals, adenosine and adenosine analogues have anticonvulsant effects that may be due to interactions with central A1 adenosine receptors. CBZ (at therapeutically relevant concentrations) inhibits the binding of agonists and antagonists to brain A1 adenosine receptors, but whether as an agonist/antagonist is not clear. The adenosine agonist, N6-[3H]cyclohexyladenosine ([3H]CHA), binds to membranes from rat cortex and hippocampus at two nanomolar binding sites or states. To clarify the actions of carbamazepine at the A1 adenosine receptor, its inhibitory actions were compared with those of known adenosine agonists and xanthine antagonists using 0.1 nM[3H]CHA, in which almost all binding is to the higher affinity state, or 10 nM [3H]CHA, in which there is a substantial contribution of binding from both states. The ratios of the IC50 values (concentration that inhibits specific binding by 50%) at 10 nM [3H]CHA to the IC50 values at 0.1 nM [3H]CHA were 18-31 for the agonists and 4-10 for the xanthine antagonists. CBZ had a ratio of 3. The inhibitory effects of GTP on [3H]CHA binding were less in the presence of the adenosine agonist, 2-chloroadenosine than were inhibitory effects in the presence of the xanthine antagonist theophylline or CBZ in both cortex and hippocampus. These in vitro studies indicate that CBZ is an antagonist at A1 adenosine receptors in cerebral cortical and hippocampal membranes from rat brain. Agonist activity at A1 adenosine receptors would have been compatible with the sedative anticonvulsant effects of CBZ, but these data do not support a role of the anticonvulsant action of carbamazepine on A1 adenosine receptors in cerebral cortex or hippocampus.

2-Chloroadenosine↗