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N Waters

Publications and source records attributed to N Waters.

6 recordsLinked to original sources
PubMed1992

The influence of serotoninergic drugs on dopaminergic neurotransmission in rat substantia nigra, striatum and limbic forebrain in vivo.

The effects of serotoninergic drugs on dopaminergic neurotransmission in the substantia nigra, the striatum and the limbic forebrain of rat have been investigated. The accumulation of 3-methoxytyramine (3-MT) following inhibition of monoamine oxidase with pargyline was used as an indirect measure of dopamine (DA) activity in vivo. The effects of the following serotoninergic drugs were tested: the 5-HT1A receptor agonist 8-OH-DPAT, the 5-HT1B receptor agonist trifluoromethyl-phenylpiperazine (TFMPP), CGS 12066 B and RU 24969, the 5-HT1A/1B antagonist (+/-)pindolol, the 5-HT2/1C receptor antagonist ritanserin, the 5-HT2/1C receptor agonist DL-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5-HT3 receptor antagonist BRL 43694, the unselective 5-HT receptor antagonist methiothepin, and carbidopa + L-5-hydroxytryptophan (L-5-HTP) to achieve a general, unselective stimulation of multiple 5-HT receptors. In the substantia nigra, carbidopa + 5-HTP treatment increased the 3-MT accumulation by 26% and decreased the DA concentration to 67% of controls, tentatively suggesting a 5-HTP-induced displacement of nigral DA. A minor, non dose-related reduction in nigral 3-MT was seen after the 5-HT1A receptor agonist 8-OH-DPAT. None of the other serotonin receptor acting drugs induced any pronounced effect on the nigral 3-MT accumulation. Taken together, the findings provide little support for the idea that one single 5-HT receptor subtype serves a modulatory function on DA activity in the substantia nigra. In the striatum and the limbic forebrain, trifluoromethyl-phenylpiperazine dose-dependently increased the 3-MT accumulation to maximally 200%-220% of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Increased dopamine release by the autoreceptor antagonist (+)-AJ 76 is Ca2(+)-dependent.

The effects of the preferential autoreceptor antagonist (+)-AJ 76 on dopamine release and metabolism were studied in the brain microdialysis model. The Ca2+ dependence of the effects of (+)-AJ 76 and d-amphetamine were compared. We found that (+)-AJ 76 increased the release and metabolism of dopamine and that the release was saturable. The release of dopamine by (+)-AJ 76 was dependent on extracellular Ca2+. However, the effects of (+)-AJ 76 on dopamine metabolism were independent of extracellular Ca2+. The effects of d-amphetamine on dopamine release and metabolism were independent of Ca2+. We conclude that the dopamine released by (+)-AJ 76 is dependent on neuronal impulse flow and that the dopamine released is of vesicular origin. The effects on dopamine metabolism and release may be exerted via different mechanisms. In contrast, the release and metabolism of dopamine by d-amphetamine were independent of impulse flow and extracellular Ca2+. We suggest that (+)-AJ 76 and d-amphetamine release dopamine from different pools.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

The putatively antipsychotic agent amperozide produces behavioural stimulation in the rat. A behavioural and biochemical characterization.

Amperozide (FG 5606; N-ethyl-4-[4',4'-bis(p-fluorophenyl)butyl]-1-piperazinecarboximide ) is a new putatively antipsychotic compound with a postulated 5-HT2 antagonistic profile. Somewhat surprisingly amperozide dose dependently induced a behavioural stimulation in reserpinized and in nonpretreated rats. The behaviour consisted of both forward and backward locomotion as well as forepaw circling and a grooming like behaviour. Since the behavioural pattern clearly differ from that produced by classical dopaminergic or serotonergic agonists (e.g. apomorphine or 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT), and has not been previously reported, we decided to investigate the origin of this effect. In the behavioural paradigms it was not possible to antagonize the amperozide stimulation in reserpinized rats with the dopamine receptor blockers haloperidol, raclopride or R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine, SCH 23390. Neither the 5-HT2 receptor blocking agent ritanserin nor the tryptophan and tyrosine hydroxylase inhibitor DL-3,4-dihydroxy-phenyl-alpha-propylacetamide, H22/54, could block the motoric stimulation or the forepaw circling behaviour produced by amperozide. However, the noradrenaline synthesis inhibitor bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulfide, FLA 63, as well as the alpha-adrenoceptor antagonist phenoxybenzamine, could partly inhibit the locomotor stimulation. Hence, noradrenaline seems to be, at least in part, involved in the behavioural stimulatory effect of amperozide. Biochemically amperozide had no effect on the dopamine synthesis rate (DOPA formation) in normal or reserpinized animals in the striatal or the limbic brain regions. In reserpinized animals amperozide also failed to antagonize the decrease in DOPA formation after apomorphine and 3-hydroxy-benzylhydrazine HCl, NSD 1015, in these regions.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1975

Random urine analyses from drug addicts in a methadone treatment programme.

Random testing of urine from opiate addicts in the methadone treatment programme at the Drug Dependency Service, Brisbane Street, Sydney, was carried out for 18 months. Six samples from each of approximately 100 clients (that is, 580 specimens) have been analysed. It was found that clients receiving high methadone dosages (80 mg and over) used illegal opiates significantly less frequently than those on lower dosages. Furthermore, a decline in the use of illegal opiates and an increase in the proportion of "clear" urine specimens (that is, clear of all drugs except methadone) were indicators of the effectiveness of the methadone programme. It was concluded that urine testing was a useful and objective means of evaluating methadone or any other drug addiction treatment programme, and of monitoring what other drugs were being taken, both consciously or inadvertently in combinations. The results of urine testing can also be of value to counsellors in the therapeutic situation.

Amphetamines↗