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Biomedical subjects

B H Westerink

Publications and source records attributed to B H Westerink.

At least 163 records · Page 9Linked to original sources
PubMed1980

Synthesis of isomeric thienobenzothiazines and their effect on dopamine metabolism in rat brain.

The synthesis of the thieno[2,3-b]-, thieno[3,4-b]- and thieno[3,2-b]benzothiazines with a hydroxyethylpiperazinylpropyl side chain and various 2 substituents is described. The influence of these neuroleptic compounds on dopamine metabolism in vivo is quantitated by determining the rise in homovanillic acid concentrations in rat corpus striatum. Notable differences in activity were found among the isomers, which were useful for structure--activity correlations in the phenothiazine neuroleptics.

Animals↗
PubMed1979

A prodrug of ADTN: selectivity of dopaminergic action and brain levels of ADTN.

The effects of administration of the prodrug dibenzoyl ADTN (DBADTN) on ADTN concentrations in rat brain and on behaviour in rats having a unilateral 6-hydroxydopamine lesion in the corpus striatum have been studied. Using a combination of HPLC and electrochemical detection as assay method it was found that there was a more selective accumulation of ADTN in the corpus striatum than in the cerebellum. In addition the accumulation of ADTN in the corpus striatum was slow in onset yet long in duration. The peak concentration of ADTN was relatively low and although it was sufficient to cause a strong stimulation of presynaptic DA receptors it did not cause significant rotation in the unilaterally lesioned rat. Prodrug methodology may thus prove useful in designing new selectively acting DA agonists.

Animals↗
PubMed1979

Do neuroleptics prevent the penetration of dopamine agonists into the brain?

A new, specific and highly sensitive method for the determination of apomorphine based on high performance liquid chromatography on a C18 reverse-phase column, coupled with electrochemical detection has been developed. The limit of detection of the assay is approximately 0.5 ng/sample (2 pmol). Haloperidol, cis-flupenthixol, metoclopramide and reserpine prevented the accumulation of apomorphine equally in "dopaminergic" as well as in "non-dopaminergic" brain areas. The non-neuroleptic trans-isomer of flupenthixol was without effect. Suppression of the accumulation of the dopamine agonist 6,7-ADTN (administered as the prodrug dibenzoyl-6,7-ADTN) was seen after combined treatment with haloperidol or reserpine, whereas cis- and trans-flupenthixol were without effect. The results imply that certain behavioural, biochemical and neuropharmacological studies, based on apomorphine in combination with other drugs, may need reinterpretation.

Animals↗
PubMed1977

On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs.

3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in the corpus striatum, nucleus accumbens and tuberculum olfactorium of the rat brain, 4 antidepressants, 4 anesthetics, dipropylacetate, ethosuximide and metoclopramide induced a rise of DOPAC and HVA levels in the 3 brain regions. No change was observed after carbamazepine, diazepam or propranolol treatment. Combined treatment with a maximally effective dose of haloperidol and morphine, oxotremorine or probenecid produced an additional rise of DOPAC and HVA levels, while no additional rise was seen with chloral hydrate, chlorimipramine, ether, halothane, metoclopramide or sulpiride. The potency of drugs to increase DA metabolism in corpus striatum relative to mesolimbic structures was estimated. Atypical neuroleptics such as sulpiride could be differentiated in this respect from classical neuroleptics such as chlorpromazine, fluphenazine and thioridazine, by their ability to produce a relatively large increase of metabolite levels in the mesolimbic regions. The heterogeneous group of 14 non-neuroleptics however produced regional changes which were very similar to those of the atypical neuroleptics. DA metabolism in mesolimbic regions, in contrast to striatal tissue, seems to respond more to atypical neuroleptics and non-neuroleptics than to typical neuroleptics.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1976

Turnover of acid dopamine metabolites in striatal and mesolimbic tissue of the rat brain.

The subject of this study was the disappearance of 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) from the brain of rats treated with pargyline and pargyline in combination with tropolone. The DOPAC decline was exponential after pargyline treatment, while the HVA decline became a first order elimination when in addition to monoamine oxidase, catechol-O-methyl transferase was also inhibited. The turnover of the metabolites was calculated by multiplying the steady state level by the fractional rate constant (k). The DOPAC turnover was found to be 23.3 nmol/g/h in the corpus striatum and 22.6 nmol/g/h in the mesolimbic structures. The HVA turnover was 11.2 nmol/g/h in the corpus striatum and 6.7 nmol/g/h in the mesolimbic structures. The data showed that under control conditions DOPAC is only partially O-methylated to HVA, while the formation of HVA via the methoxytyramine pathway is unlikely. DOPAC turnover therefore probably approximates dopamine turnover.

3,4-Dihydroxyphenylacetic Acid↗