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Biomedical subjects

N S Shah

Publications and source records attributed to N S Shah.

At least 37 records · Page 2Linked to original sources
PubMed1979

Neurolepticlike actions of l-methadone: effect on mescaline-induced altered behavior and on tissue levels of mescaline in mice.

Mice were injected ip with either saline, l-methadone (2.5, 5, 20 mg/kg), perphenazine (1, 10, 15 mg/kg), or chlorprothixene (1.25, 2.5, 15 mg/kg) 30 min prior to mescaline-14C (25 mg/kg). Mescaline-induced behavioral changes such as agitation, excitement, slight increase in ventilation, and fright to sound stimuli were prevented by all doses of three drugs, and head-shaking, scratching, and locomotor-increasing effects by 5 and 20 mg/kg methadone and by all doses of both neuroleptics. Catalepticlike state and moderate to marked hypothermia induced by all doses of chlorprothixene, 10 and 15 mg/kg perphenazine, and 20 mg/kg methadone were not reversed by mescaline. Chlorprothixene (all doses), perphenazine (10, 15 mg/kg), and methadone (5, 20 mg/kg) caused marked retention of mescaline and its deaminated metabolite, 3, 4, 5-trimethoxyphenyl acetic acid in both brain and plasma. The fact that relatively higher doses of methadone than neuroleptics are needed to ensure effective antagonism to mescaline action tends to indicate a less specific interaction of the opiate with the neuroleptic/dopamine receptor proposed for central mescaline effects.

Animals↗
PubMed1978

Behavioral effects and metabolic fate of N,N-dimethyltryptamine in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), improniazid and chlorpromazine.

Behavioral aspects and metabolic fate of N,N-dimethyltryptamine (DMT) were studied in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), iproniazid or chlorpromazine (CPZ). DMT at doses of 2.5, 10.0, and 25.0 mg/kg produced several behavioral changes in a dose-related manner: inhibition of spontaneous locomotor movement, enhanced fright responses to sound stimuli, trembling, head twitching, inco-ordinated movements of hind-legs, flat or extended tail and abnormal posture with the extension of hind-legs. Pretreatment with ipromazid (153 mg/kg; 4 hr) but not SKF 525-A (50 mg/kg; 1 hr) prolonged the behavioral effects produced by 2.5 mg/kg DMT while CPZ (15 mg/kg; 0.5 hr) completely abolished the responses induced by 25 mg/kg DMT. Earlier behavioral effects generally coincided with the brain concentrations of DMT. Dose-dependent increases with rapid uptake and disappearance in the brain, plasma and hepatic levels of DMT were measured with doses of 10 and 25 mg/kg DMT. Iproniazid but not SKF 525-A markedly enhanced tissue levels of DMT. it is concluded that DMT is metabolized chiefly by monoamine oxidase rather than by drug-metabolizing hepatic microsomal enzymes and that DMT-induced behavioral effects are due to the parent compound rather than its metabolite.

Animals↗
PubMed1978

Placental transfer and tissue distribution of dextro-amphetamine in the mouse.

3H-d-amphetamine (5 mg/kg, free base) was injected i.p. to male and non-pregnant female mice and to pregnant female mice on day 16 of gestation. The tissue levels of amphetamine were examined as a function of time. Peak concentrations in matured tissues occurred at 15 min, those in placenta, whole fetus, fetal brain and liver at 1 hr. No notable differences were detected in tissue levels of amphetamine in males and non-pregnant females. Disappearance of amphetamine from tissues of pregnant animals was slower than those of other groups. At 15 min, the fetal brain and liver accumulated 1/6 amounts of amphetamine compared to corresponding maternal tissues. Pregnant animals excreted significantly lower amount of total radioactivity compared to non-pregnant females. It is concluded that amphetamine was transported across the placenta and that the lower concentrations in fetal tissues compared to maternal tissues appear to be due to several physico-chemical factors that regulate the transplacental transfer of a foreign chemical compound.

Animals↗
PubMed1978

Regional localization of methaqualone in rat brain.

Distribution of orally administered methaqualone-14C (25 mg/kg) in several rat brain areas was examined. Peak concentration attained at 1.5 hr. Among brain areas, highest concentration was measured in pineal gland (8.2 microgram/g). MTQ levels in the cortex, pituitary, hypothalamus and hippocampus ranged from 3 to 3.5 microgram/g, those in the mid-brain, medulla-pons, striatum and cerebellum from 2 to 2.5 microgram/g. Significant amounts of MTQ in all brain regions were still present at 3 hr. These results indicate that MTQ was somewhat uniformly distributed in various brain regions as a result of its lipophilic nature.

Animals↗
PubMed1977

3H-metaraminol releasing action of mescaline from rat hypothalamus in vitro.

The amine releasing action of mescaline was investigated in rat isolated hypothalamus labeled with 3H-metaraminol. Mescaline had no effect on the uptake of 3H-metaraminol but produced its release in a concentration-related manner. 4 x 10(-4) M mescaline, which produced submaximal effects was used for subsequent experiments. 3 x 10(-5) M cocaine had no effect on the 3H-metaraminol releasing action of mescaline. Mescaline was fully effective in Ca2+-free medium while 6 x 10(-2) M KCl was ineffective. 3 x 10(-7) M tetrodotoxin or 6 x 10(-5) M lidocaine partially blocked mescaline-induced release but substantially or completely blocked 3 x 10(-2) M KCl-induced release. Prior exposure of hypothalamus to 3 x 10(-4) M tyramine reduced the releasing action of mescaline. Thus, mescaline appears to release 3H-metaraminol both by Ca2+-independent (tyramine-like) and Ca2+-dependent (lidocaine-sensitive) mechanisms. 3 x 10(-4) M tyramine and 6 x 10(-2) M KCl released 14C from control hypothalamus labelled with 14C-mescaline, but not from reserpinized hypothalamus. The amounts of 14C recovered in 14C-mescaline labeled control and reserpinized hypothalamus at the end of 50 min of efflux were similar suggesting a poor retention of 14C-mescaline by storage particles.

Animals↗
PubMed1977

Amine releasing action of nicotine from rat hypothalamus in vitro.

Nicotine released 3H-radioactivity from rat hypothalamus labeled with 3H-metaraminol (3H-MA) in a concentration-related manner. The release was not blocked by hexamethonium (1.8 x 10(-5)M - 2.3 x 10(-3)m), tetrodotoxin (3 x 10(-7)M), lidocaine (6 x 10(-5)M or Ca++-free medium. Cocaine (3 x 10(-5)M) blocked the releasing action of nicotine. Nicotine failed to release 3H-MA in tissue exposed to tyramine. It is concluded that the nicotine-induced release of 3H-MA is intracellular.

Animals↗
PubMed1976

Effects on rectal temperature in rats of gamma-aminobutyric acid; possible mediation through putative transmitters.

The rectal temperature of male rats was measured in a thermoneutral environment (25 degrees C) and at ambient temperatures of 15 and 35 degrees C. Unless otherwise specified all drugs were administered intracerebroventricularly (i.c.v.) and all results are reported for the thermoneutral environment. Exposure to 15 degrees C did not affect the rectal temperature but exposure to 35 degrees C produced hyperthermia. At 15 and 25 degrees C, 20 mug GABA produced hyperthermia which was longer lasting at the former ambient temperature. GABA (20 mug) prevented the hyperthermic effect of exposure to 35 degrees C and produced hypothermia in animals maintained at this temperature for 1 hr. A low dose (1 mug) of NA produced hyperthermia and a higher dose (mug) hypothermia. In rats pretreated with sodium salicylate (i.p.), 20 mug GABA and 1 mug NA produced hypothermia instead of hyperthermia, suggesting the release of PGE in mediating hyperthermia. The hypothermic effect of 10 mug NA and of GABA observed at 35 degrees C was blocked by phentolamine, an indication of the possibility of alpha-adrenoceptor mediation.

Aminobutyrates↗
PubMed1976

Uptake of 3,4-dimethoxyphenylethylamine-1-14C (14C-DMPEA) by rat tissues in vitro.

Rat heart and spleen slices were incubated with 3,4-dimethoxyphenylethylamine-1-14C(14C-DMPEA) in Krebs medium at 37 C. At the end of 5-20 min of incubation, the heart did not take up the radioactivity while the spleen did. The Km and Vmax values of uptake in the spleen were 1 x 10(-4) M and 20 nmole/g per min, respectively, and the uptake was reduced to 16.0-35.1% in the cold (4 C) and to 40.3-64.0% in Na+-free medium. Thus, the uptake was an energy-dependent active process but was only partially Na+-dependent. Spleen slices incubated with 14C-DMPEA-free medium for 15 min following incubation with 14C-DMPEA retained 41.0-74.8% of radioactivity. The uptake was insensitive to norepinephrine (0.313 and 0.939 muM), dopamine (9.98 muM), 5-hydroxytryptamine (5 muM), cocaine (14.8 muM), 1-amphetamine (0.3 and 300 muM), d-amphetamine (300 muM), and normetanephrine (45.7 muM). 6-Hydroxydopamine treatment of rats, which produced 93% reduction in the splenic norepinephrine content, did not significantly reduce uptake. Thus, the uptake of DMPEA into the spleen is not by adrenergic neurones.

Amphetamine↗
PubMed1976

Tissue distribution of levo-methadone in nonpregnant and pregnant female and male mice: effect of SKF 525-A 1,2.

Male, nonpregnant and pregnant female (15-17 gestational days) mice were injected i.p. with saline or SKF 525-A (50 mg/kg) and 1 hour later with levo-3H-1-methadone (205 mug/kg; 0.8 and 5 mg/kg). Levels of free methadone were examined in some or all of the following tissues: brain, plasma, liver, lung, spleen, kidney, heart, eye, placenta, amniotic fluid, whole fetus, fetal brain and liver. In saline controls, the methadone concentrations in several adult tissues, whole fetuses, fetal brain and liver reached peak levels at 15 minutes and were negligible at 24 hours. Tissue levels of methadone increased in a dose-related manner; however, the brain/plasma concentration ratios with the three doses were almost unity at 15 minutes, 1 hour and 3 hours. Among adult tissues with high concentrations were the lung, liver, kidney and spleen; the brain in contrast contained very low concentrations. No notable differences were detected in the tissue levels of methadone in males and nonpregnant females; however, in pregnant mice significantly higher levels were observed in the lung and the liver. Fetal brain, liver and whole fetus concentrations were approximately similar. At 15 minutes, the fetal brain contained about 3 times more methadone than the maternal brain and the difference increased at subsequent times. Nonpregnant females excreted somewhat larger amounts of 3H in the urine than did pregnant females. SKF 525-A markedly enhanced and prolonged the concentrations of methadone in all the adult and the fetal tissues and lowered urinary excretion of total radioactivity in nonpregnant and pregnant females. Marked increases in tissue radioactivity after SKF 525-A might be due to a combination of effects involving inhibition of drug metabolism, altered tissue distribution and lower urinary excretion.

Animals↗
PubMed1975

Studies on accumulation of (14C)-mescaline in brain homogenates: effects of psychotropic and other agents.

Incubation of rat brain homogenates or 14,500 g pellet isolated from the homogenate with (14C)-mescaline was associated with accumulation of (14C)-mescaline in the pellet. 1.33 mumol/ml of chlorpromazine, trifluoperazine, fluphenazine, imipramine, desmethylimipramine, nortriptyline and amitriptyline inhibited the accumulation of mescaline. Lower concentrations (0.133-0.44 mumol/ml) of the psychotropic drugs were less effective. The tricyclic antidepressants were less potent than the tranquilizers. Although the trimethoxyphenylacetic acid (TMPA) levels of the pellet were also reduced by the psychotropic drugs, the TMPA:mescaline ratios were unchanged indicating that the drugs had no effect on the metabolism of mescaline. The inhibition of accumulation of mescaline by the high concentrations of tranquilizers may divert more of the hallucinogen to the receptor site. Thus, an explanation for the reported worsening of clinical syndrome of hallucinogenic poisoning by tranquilizers is provided.

Animals↗
PubMed1975

Interaction of mescaline with phenothiazines: effect on behavior, body temperature, and tissue levels of hallucinogen in mice.

Mescaline (25 mg/kg; 66 muc/kg) was injected (ip) in mice 45 min before chlorpromazine (CPZ, 2.5, 5, 15 mg/kg), thioridazine (10, 30, 45 mg/kg), or chlorpromazine-sulfoxide (CPZ-SO, 15 mg/kg). Excitement, agitation, slight increase in ventilation and occasional head-shaking were seen 30 min after mescaline and continued for 30-45 min thereafter; locomotor activity and the number of scratching events were significantly increased during this period. CPZ (2.5, 5, 15 mg/kg) and thioridazine (10, 30, 45 mg/kg) partially or completely blocked mescaline-induced gross behavior; CPZ-SO (15 mg/kg) was not effective. Increased scratching responses and locomotor activity induced by mescaline were antagonized by all doses of CPZ and thioridazine; at higher doses, both CPZ (7.5, 15 mg/kg) and thioridazine (45 mg/kg) induced cataleptic-like condition and marked hypothermia. Tissue levels of mescaline, examined 3 hr after its administration, were increased by all doses of CPZ and a higher dose of thioridazine (45 mg/kg); CPZ-SO and lower doses of thioridazine had no effect.

Animals↗