PubMed Health⌕ Search

Biomedical subjects

J Mott

Publications and source records attributed to J Mott.

At least 37 records · Page 2Linked to original sources
PubMed1987

A biochemical basis for psychotic symptoms in patients with brain dysfunction.

Thirteen brain dysfunctional patients with psychosis were compared to 11 brain dysfunctional patients without psychosis by EEG, CT scan and neuropsychological test abnormalities, and abnormalities in serine metabolism. None of the tests of conventional measures of brain pathology and pathophysiology significantly differentiated between the psychotic and nonpsychotic patients; only the last measure which has previously been shown to be a biochemical vulnerability factor for psychosis, was significantly different in the two groups. This study suggests that the brain pathology and pathophysiology per se are not significant factors that make such patients psychotic, but these patients are vulnerable to psychosis because of a biochemical abnormality.

Adult↗
PubMed1986

Effects of glutaminase inhibition on release of endogenous glutamic acid.

The effects of four inhibitors of glutamine hydrolysis on synaptosomes derived from several regions of the brain were studied. The calcium-specific release of endogenous glutamic acid was determined in the presence of varying concentrations of 6-diazo-5-oxo-norleucine (DON), N-ethyl-maleimide (NEM), 2-chloroadenosine (2-CA) or haloperidol. Both DON and NEM reduced the calcium-specific release in a concentration-dependent manner, equally in all regions tested. 2-Chloroadenosine also decreased release and the effect was most evident in the amygdala. As reported earlier, haloperidol blocked release of glutamic acid only in the amygdala. In synaptosomes from the amygdala, both DON and NEM failed to affect the calcium-specific release of aminobutyric acid (GABA), glycine or serotonin at concentrations which reduced release of glutamate by 50%; NEM, but not DON, elevated the release of dopamine. Dopamine itself affected neither the release of glutamate nor its blockade by haloperidol even in extremely large concentrations.

2-Chloroadenosine↗
PubMed1986

Drug effects on serine metabolism in psychiatric patients.

The question of whether neuroleptics can play a role in the hyperserinemia and low serine hydroxymethyltransferase (SHMT) activity previously reported in psychotic patients is investigated in this report. We find that in drug-free psychotics who had significantly higher plasma serine levels (PSL) and lower SHMT activity compared to nonpsychotics and normal subjects, more than 2 weeks of neuroleptic treatment decreased PSL and did not affect SHMT activity. This finding makes it unlikely that neuroleptics play an important role in the hyperserinemia of psychotics. The possible role of dietary factors in these patients is also discussed.

Antipsychotic Agents↗
PubMed1985

Amphetamine stimulation of glutaminase is blocked by neuroleptics.

The ability of several classes of neuroleptics to inhibit the activity of phosphate-activated glutaminase was studied in several brain regions. These agents decreased glutaminase activity only in the amygdala. Amphetamine elevated glutaminase activity in this region. This stimulation was not blocked by (-) butaclamol, but was blocked by (+) butaclamol, haloperidol, chlorpromazine or clozapine.

Amphetamine↗
PubMed1985

Metabolism of an ingested serine load in psychotic and nonpsychotic subjects.

Our previous studies have shown that in psychotics, the plasma serine level is abnormally high and that plasma serine hydroxymethyltransferase (which cleaves serine to glycine) activity is abnormally low as compared with that in nonpsychotic subjects. In this study, psychotic and nonpsychotic subjects ingested a large bolus of L-serine (4 mM/kg) at breakfast and blood was drawn before breakfast, 2 hr, 4 hr, and 6 hr after serine ingestion. Baseline serine and SHMT activity differentiated between psychotics and nonpsychotics with high degrees of significance (p less than 0.0001) and p less than 0.01, respectively). Plasma serine levels 2 hr after serine ingestion were significantly higher (p less than 0.01) in nonpsychotics as compared with psychotics. Elimination of serine in psychotics was bimodal and was significantly different from that of nonpsychotics (p less than 0.0079, Moses test). These findings provide additional evidence for abnormal serine metabolism in psychotic patients.

Age Factors↗
PubMed1985

Differentiation of psychotic from nonpsychotic depression by a biological marker.

In a study of fasting plasma serine levels (PSL) previously shown to be a biological marker for psychosis, we found significantly higher (P = 0.0008) PSL in 18 psychotic depressives when compared to 22 nonpsychotic depressives. Similarly the activity of the enzyme serine hydroxymethyltransferase (SHMT) which cleaves serine to glycine, was significantly lower (P less than 0.0001) in psychotics than in nonpsychotics. The difference between psychotic and nonpsychotic depressives were not attributable to age, sex or drug intake. This finding is in support of the hypothesis that these two types of depressions are qualitatively distinct from each other.

Adult↗
PubMed1985

Speech perception ability and psychophysical tuning curves in hearing-impaired listeners.

Performance-intensity functions for monosyllabic words were obtained as a function of signal-to-noise ratio for broadband and low-pass filtered noise. Subjects were 11 normal-hearing listeners and 13 hearing-impaired listeners with flat, moderate sensorineural hearing losses and good speech-discrimination ability (at least 86%) in quiet. In the broadband-noise condition, only small differences in speech perception were noted between the two groups. In low-pass noise, however, large differences in performance were observed. These findings were correlated with various aspects of psychophysical tuning curves (PTCs) obtained from the same individuals. Results of a multivariate analysis suggest that performance in broadband noise is correlated with filter bandwidth (Q10), while performance in low-pass noise is correlated with changes on the low-frequency side of the PTC.

Adolescent↗
PubMed1984

Direct effect of neuroleptics on glutamate release.

In studies designed to assess the pre-synaptic effects of neuroleptics in vitro, synaptosomes were prepared from several regions of rat brain. These preparations were incubated in the presence of a representative of each of the major classes of neuroleptic--chlorpromazine, haloperidol, or clozapine, or with (+) or (-)butaclamol. The calcium-specific release of endogenous glutamic acid was reduced only in synaptosomes derived from the amygdala. In this area, each of these agents [except (-)butaclamol] reduced the release of glutamic acid to a maximum of 40% in a concentration-dependent manner. When [3H]glutamine was included in the incubation media, a reduction in the released [3H]glutamate was present with 10(-8) M haloperidol, and 5 X 10(-8) M (+)butaclamol, clozapine, or chlorpromazine. (-)Butaclamol was inactive at 10(-5) M, a concentration producing complete blockade of the release of [3H]glutamic acid when active agents were included. Again, the effects were observed only in the amygdala. All agents, including (-)butaclamol blocked the uptake of [3H]glutamine into depolarized synaptosomes.

Amygdala↗
PubMed1984

Potential locus and mechanism of blockade of conditioned avoidance responding by neuroleptics.

In order to assess the possible loci of action of neuroleptics in blocking the acquisition of a one-way conditioned avoidance response, microinjections of three neuroleptics and seven putative neurotransmitters were made into several brain regions and their effects on this behavior were assessed. When injected into the amygdala, the ED50 values for haloperidol (0.128 nmol), chlorpromazine (1.04 nmol) and thioridazine (1.41 nmol) were appropriate in relation to their clinical potency. Injections of neurotransmitters were without effect except in a few cases. Most significantly, the intra-amygdaloid administration of glutamate diethyl ester (an antagonist at quisqualate-type receptors) produced a blockade of avoidance acquisition which, as in the case of the neuroleptics, was not diminished by pretreatment with atropine. Following intraperitoneal injection of chlorpromazine, a statistically-significant blockade of avoidance acquisition and of glutamate, released from slices of amygdala, was obtained at doses of 2 mg/kg or more. With haloperidol, comparable behavioral effects and release of glutamate were found at doses of 0.05 mg/kg or more. The depression of release of glutamate from amygdaloid slices could be attributed to glutamate derived from glutamine. These data suggest a possible role for glutamatergic transmission in the effects of neuroleptics.

Amygdala↗
PubMed1984

Serine metabolism and psychosis.

Plasma serine levels (PSL) in a group of patients with the diagnosis of major or atypical psychoses were significantly higher than in patients with nonpsychotic diagnoses or nonpatient controls. The enzyme serine hydroxymethyltransferase (SHMT), which metabolizes serine to glycine, showed abnormal activity in the psychotics compared to nonpsychotics and controls. PSL differentiated psychotics from nonpsychotics with a high (95%) degree of confidence. PSL were highly correlated to SHMT activity, suggesting that the hyperserinemia in psychotics was due to the abnormality of the enzyme. Previously psychotic patients who had been treated and were psychosis free still manifested abnormal high PSL and abnormal enzyme activity. These findings suggest that disturbed serine metabolism may be a biological marker and a vulnerability factor for psychosis.

Adult↗
PubMed1983

RDS-127 (2-di-n-propylamino-4,7-dimethoxyindane): central effects of a new dopamine receptor agonist.

Apomorphine (APO), 2-di-n-propylamino-4,7-dimethoxyindane (RDS-127) and 2-di-n-propylamino-5,8-dimethoxytetralin (JMC-181) were examined on a variety of biochemical and pharmacological assays to determine their possible interaction with dopamine (DA) receptors. Nanomolar concentrations of all three compounds displaced [3H]APO from specific high-affinity binding sites in rat striatal membrane preparations, while higher concentrations were required to displace [3H]spiperone or [3H]rauwolscine. APO caused a concentration-dependent increase in the ability to stimulate postsynaptic DA receptors associated with adenylate cyclase (D1-sites) in the carp retina, whereas RDS-127 or JMC-181 were inactive in concentrations up to 300 microM. APO was very active in causing contralateral turning behavior in rats with a 6-hydroxydopamine lesioned substantia nigra (SN); RDS-127 was approximately 8 times less potent in producing contralateral rotations and JMC-181 was inactive. RDS-127 produced biphasic, dose-related changes in rat spontaneous locomotor activity similar to that reported for APO. The locomotor stimulant effects of RDS-127 were 3 times more potent and 4 times greater in duration than that induced by APO. JMC-181 produced primarily sedation in the doses tested. APO, RDS-127 and JMC-181 were active in inhibiting the accumulation of dopa in the caudate nucleus and olfactory tubercle using the in vivo gamma-butyrolactone procedure; 5-hydroxytryptophan accumulations were not altered significantly. RDS-127 was 7 times more potent than APO in inhibiting dopa accumulation in the caudate nucleus and equipotent to APO in the olfactory tubercle. Dopa accumulation was weakly inhibited by JMC-181. When single unit extracellular action potentials were recorded from purported DA-containing neurons in the SN, RDS-127 decreased the firing of neurons in the pars compacta of SN (ID100 = 40 +/- 10 nmol/kg i.v.). In contrast, firing of units in the pars reticulata of SN were not altered or increased in response to RDS-127. The biochemical electrophysiological and behavioral effects of RDS-127 were blocked or reversed by DA receptor antagonists. These data indicate that RDS-127 is significantly more selective than APO in preferentially activating DA autoreceptors as opposed to the postsynaptic DA receptors in the nigrostriatal pathway. The possibilities of designing potent, long acting, nonergot, noncatechol-containing DA receptor agonists are discussed.

5-Hydroxytryptophan↗
PubMed1982

2-Amino-4,7-dimethoxyindan derivatives: synthesis and assessment of dopaminergic and cardiovascular actions.

N-Alkylated derivatives of 2-amino-4,7-dimethoxyindan were prepared for evaluation of central and peripheral dopaminergic activity using biochemical and behavioral tests in the rat and cardiovascular responses in the cat. 2-(Di-n-propylamino)-4,7-dimethoxyindan (4e) demonstrated equal activity with apomorphine to activate peripheral presynaptic dopamine receptors. Central pre- and postsynaptic dopamine receptors were also activated with 4e. In contrast to the intense long-acting sympathomimetic actions previously reported for the 2-amino-5,8-dimethoxytetralins, these compounds produced weak, transient effects in heart rate and blood pressure. The majority of 2-amino-4,7-dimethoxyindan derivatives tested are weak or inactive pre- and postsynaptic dopamine receptor agonists.

Animals↗
PubMed1982

Effects of semirigid methoxamine analogs on vascular smooth muscle: studies of methoxy-2-aminotetralin and 2-aminoindane derivatives.

The effects of semirigid methoxy analogs of 2-aminotetralin (2-AT) and 2-aminoindane (2-AI) were studied on superfused dog metatarsal veins to investigate postjunctional interactions produced by these agents on sympathetically innervated vascular smooth muscle. The following compounds were tested: norepinephrine (NE); serotonin (5-HT); amphetamine (AMP); methoxamine (MTH); 2-di-n-propylamino-4,7-dimethoxyindane (RDS-127); 2-di-n-propylamino-5,6,-dimethoxyindane (JPC-211); 2-di-n-propylaminoindane (JPC-6036); 2-methylamino-5,8-dimethoxytetralin (DR-31); 2-methylamino-4,7-dimethoxyindane (RDS-31). The results of this study indicate that contractions produced by these compounds have the following ranked ordered potencies: 5-HT greater than NE much greater than MTH greater than or equal to RDS-127 = DR-31; JPC-6036, RDS-31, JPC-211 and AMP were inactive. The contractions produced by NE, MTH, RDS-127 or DR-31, but not 5-HT, probably occur through alpha1-adrenergic receptors since these contractions were blocked with prazosin. 5-HT and RDS-127, but not NE, MTH or DR-31 activate serotonin receptors since methysergide blocked the response produced by 5-HT or RDS-127. NE-induced contractions were augmented and tyramine-induced contractions were attenuated with cocaine. The responses of MTH, RDS-127 or DR-31 probably do not displace NE through a tyramine-like action since cocaine had no effect on contractions induced by these compounds. These data suggest that semirigid paramethoxylated derivatives of 2-AT and 2-AI are potent postjunctional receptor agonists which probably initiate venoconstriction via direct receptor interactions. The structure-activity relationships of these compounds are discussed.

Animals↗
PubMed1982

Structure-activity relationships of 2-aminotetralins and 2-aminoindanes: inhibitory neuroeffector mechanisms in isolated guinea-pig ilea.

The ability of 2-aminotetralins (2-ATs), 2-aminoindanes (2-AIs), morphine (M) and clonidine (CLON) to alter neuroeffector transmission was studied on field-stimulated (FS) guinea-pig ilea (GPI). The activity of these compounds to inhibit K+, histamine (H), actylcholine (ACh), nicotine (Nic) and serotonin (5-HT) induced contractions was determined using superfused GPI segments. 2-ATs, 2-AIs, M and CLON dose-dependently inhibited contractions produced by low frequency stimulation through alpha-adrenergic, opioid or unknown receptor mediated mechanisms. 2-ATs inhibited ACh, Nic, 5-HT and FS, but not K+- or H-induced contractions. 2-ATs, 2-Ais and M were more potent than hexamethonium in inhibiting Nic-induced contractures. 2-AT and 2-AI-induced inhibition was not antagonized by naloxone or phentolamine. However, the inhibitory effects of 2-ATs. 2-AIs and M on FS-GPI were antagonized by increasing the concentration of Ca2+ ion in the media. These data are consistent with the supposition that 2-ATs, 2-AIs or M alter neuroeffector transmission through competitive changes in Ca2+ disposition in cholinergic neurons of guinea-pig isolated ilea. A discussion relating other biological actions of 2-ATs or 2-AIs (e.g. alpha-adrenergic mediated antinociception) to the observed inhibitory neuroeffector responses is provided.

Acetylcholine↗
PubMed1980

Sedative and analgesic actions of methoxylated 2-aminotetralins; involvement of alpha 1- and alpha 2-adrenoreceptors.

Three 5,8-dimethoxylated derivatives of 2-aminotetralin (2-AT) were compared with clonidine, methoxamine and phenylephrine in tests for sedation (inhibition of exploratory activity) and analgesia. In both tests the 2-AT derivatives were less potent than clonidine, but more potent than methoxamine or phenylephrine. Antagonism of the 2-AT derivative, DR-31, and clonidine by yohimbine in both tests argues for the involvement of alpha 2-adrenoreceptors in the mediation of these behavioral effects. alpha 1-Adrenoreceptors may also mediate an inhibition of exploratory activity since the inhibition induced by methoxamine was antagonized by phenoxybenzamine (POB) but not by yohimbine. The methoxylated 2-AT derivatives, which have previously been shown to exert potent peripheral alpha 1-agonism are now demonstrated to have sedative and analgesic effects characteristic of central alpha 2-adrenergic stimulation.

Analgesics↗
PubMed1979

The validity of addict notifications.

Two representative samples of males first notified as addicts during 1969, one by hospitals and the other by penal establishments, were followed up for five years. It was found that 95 per cent of the hospital sample, but only 30 per cent of the penal sample, were addicted to opiates at some time during this follow-up, as judged by Home Office records. Notification may depend as much upon the setting and circumstances in which doctors see their patients as on their clinical judgement of a 'notifiable' case of addiction.

Heroin Dependence↗