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Biomedical subjects

R T Coutts

Publications and source records attributed to R T Coutts.

At least 145 records · Page 8Linked to original sources
PubMed1985

Reserpine-induced hypothermia and its reversal by dopamine agonists.

Prior treatments with reserpine altered the thermic response of mice to subsequently administered apomorphine and amphetamine. Thus, normal mice exhibited hypo- and hyper-thermic responses to apomorphine and (+)-amphetamine, respectively but did not respond to (-)-amphetamine. These responses were each readily attenuated by haloperidol. Reserpinized mice, on the other hand, exhibited hyperthermic responses to all three agonists and these responses were not attenuated by haloperidol. In addition to its hypothermic action, reserpine also produced hypoactivity which was reversed by (+)-amphetamine. This reversal of hypoactivity was attenuated by haloperidol. These data suggest that reversal of reserpine-induced hypothermia by dopamine agonists results through activation of mechanisms which are separate from those normally associated with agonist-induced thermic responses. Reversal of hypoactivity, on the other hand, appears to be due to reactivation of those systems which normally regulate locomotor activity.

Amphetamine↗
PubMed1985

Comparison of the effects of amphetamine and a fluorinated analogue on locomotion and exploratory activity in the mouse.

(+)-Amphetamine (AM) and its fluorinated analogue (+)-2-amino-3-fluoro-1-phenylpropane (fluoroamphetamine, FAM) were compared with regard to their effects on locomotor and exploratory activity in mice. Both drugs caused a reduction in spontaneous exploration, but this effect was more marked with FAM than with AM at 1 h after injection. Both compounds increased locomotor activity 10 min after injection, but FAM had sedative effects after 1 h, while AM continued to be stimulatory.

Amphetamine↗
PubMed1984

Determination of amphetamine, norephedrine, and their phenolic metabolites in rat brain by gas chromatography.

A specific analytical procedure for the quantitation of amphetamine (I), norephedrine (III), and their amphoteric metabolites, p-hydroxy-amphetamine (II) and p-hydroxynorephedrine (IV), in biological samples using electron-capture gas chromatography (GC-EC) is described. The procedure utilizes the ion-pairing reagent, bis(2-ethylhexyl)phosphoric acid, which frees the amines from most contaminants and permits the efficient extraction of the amphoteric compounds (as acetates) from the aqueous solution. Amines I and III and acetylated amines II and IV were perfluoroacetylated prior to GC-EC analysis. Metabolism of I, II, and III in the rat brain was studied. Results indicate that both in vivo and in vitro amines I and III are p-hydroxylated to II and IV, respectively, and II is beta-hydroxylated to give IV. Norephedrine (III) was not detected as a rat brain metabolite of amphetamine (I).

Amphetamine↗
PubMed1984

P-chloroamphetamine and a side-chain fluorinated analog: effects on brain amine levels and behavior.

Reserpinized (1 mg/kg, IP-24 hr) and saline-pretreated male rats were subdivided into groups receiving p-chloroamphetamine (pCA, 5.2 mg/kg, IP), 1-fluoromethyl-2-p-chlorophenylethylamine (FpCA, 5.6 mg/kg, IP), or saline, 90 minutes before the testing of behavior in the open-field and 150 minutes before sacrifice for assay of brain levels of amines. FpCA and pCA produced identical investigative and social patterns of behavior in saline pretreated animals in spite of the fact that pCA reduced serotonin levels whereas FpCA did not. Both pCA and FpCA enhanced dopamine and noradrenaline levels compared to saline controls. The behavioral syndrome common to FpCA and pCA animals was one of increased sitting still, and decreased locomotion and self-grooming while alone, and decreased locomotion, and social behavior but increased sniffing of the environment while in the company of an untreated male rat. Reserpine pretreatment exacerbated this syndrome of inactivity in pCA more than in FpCA rats even though the reserpinized groups did not differ from each other in the concentrations of the three amines.

Amphetamines↗
PubMed1984

Rat brain concentrations of 5-hydroxytryptamine following acute and chronic administration of MAO-inhibiting antidepressants.

Groups of male Sprague-Dawley rats were injected once daily with phenelzine (15 mg/kg) or tranylcypromine (10 mg/kg) and killed 6 h after drug administration on days 1, 2, 8 and 19. Brains were analyzed for MAO activity by a radiochemical procedure and for 5-HT concentrations by an electron-capture gas chromatographic procedure. Both drugs affected 5-HT concentrations in a similar manner--a significant increase of 5-HT over control levels by day 1, with levels still increasing between days 8 and 19, having attained concentrations approximately 5 times control values by day 19.

Animals↗
PubMed1984

Brain levels of 5-hydroxytryptamine, tryptamine and 2-phenylethylamine in the rat after administration of N-cyanoethyltranylcypromine.

Brain levels of 5-hydroxytryptamine (5-HT), tryptamine (T), 2-phenylethylamine (PEA) and monoamine oxidase activity at 5, 15, 30, 60, 120 and 240 min were determined in male Sprague-Dawley rats after intraperitoneal injection of the "pro-drug" N-2-cyanoethyltranylcypromine (CE-TCP, dose 0.1 mMole/kg). Analyses of 5-HT, T and PEA were performed on an electron-capture gas chromatograph with a capillary column. Activity of MAO-A and MAO-B was measured using a radiochemical method. Results indicate substantial inhibition of MAO in rat brain after intraperitoneal administration of CE-TCP, leading to elevated levels of 5-HT, T and PEA as early as 5 min after drug administration. Increases in brain levels of the trace amines T and PEA were much greater (approximately 40 and 100 times control levels, respectively) than with 5-HT (approximately 1.8 times control level) 240 min after administration of CE-TCP.

Animals↗
PubMed1984

Effects of chronic phenelzine in the rat: altered tissue weights and metabolism of 14C-phenelzine.

Phenelzine (2-phenylethylhydrazine, PZ, Nardil) a clinically important antidepressant, inhibits several enzyme systems including monoamine oxidase (MAO). Since PZ is itself a known substrate for MAO, it is possible that its metabolites will differ according to the functional status of MAO. We have, therefore, examined aspects of the metabolism of 14C-PZ in the rat after multiple (15 days) treatments with nonlabelled PZ and compared results to those obtained from drug naive animals. In addition, we have examined the effects of PZ treatment upon total body weight and the weights of selected organs. Total body weights and weights of lungs, livers and kidneys were reduced from controls after repeated injection with PZ. The excretion of radioactivity was also altered. The PZ-pretreated animals excreted less (p less than 0.05) radioactivity in urine (41.1 +/- 5.6 vrs 59.2 +/- 3.7% of dose in controls) and more in expired air (p less than 0.05) than did controls. These data suggest that prior treatments with PZ alter the metabolism and excretion of subsequently administered 14C-PZ.

Animals↗
PubMed1984

Displacement of serotonin from binding sites in rat cortex: the effects of biogenic "trace" amines.

The concentrations for 50 percent inhibition of binding (IC50's) to specific in vitro serotonin binding sites (5-HT1 and 5-HT2) of rat cerebral cortex were determined for the trace amines 2-phenylethylamine, m- and p-tyramine, tryptamine, and (+)- and (-)- alpha-methyltryptamine. Tryptamine gave an IC50 of 66.7 +/- 4.8 nM (n = 7) at the 5-HT1 site and an IC50 of 3.85 +/- 0.16 microM (n = 7) for the 5-HT2 binding site. The IC50 values for all the other compounds were in the micromolar range and were different at the two binding sites except for p-tyramine (IC50, 5-HT1 = IC50, 5-HT2 = 17 microM. The trace amines may have different functional roles as evidenced by their different degrees of displacement of serotonin at 5-HT1 and 5-HT2 binding sites in the brain.

Animals↗
PubMed1984

A rapid and sensitive gas chromatographic method for quantitation of 2-phenylethylamine in brain tissue and urine.

A rapid, sensitive procedure for analysis of 2-phenylethylamine in brain tissue and urine is described. The method involves extraction with a liquid ion exchanger, elution with HCl, acetylation under aqueous conditions, pentafluorobenzoylation under anhydrous conditions and analysis using a gas chromatograph equipped with a capillary column and an electron-capture detector.

Animals↗
PubMed1983

Some in vivo responses to a side chain monofluorinated amphetamine in the rat.

Mature male or female Sprague-Dawley rats were injected intraperitoneally with various doses (0.005, 0.027 and 0.05 mM/Kg) of (+) amphetamine sulfate or (+)-alpha-fluoromethyl-beta-phenylethylamine hydrochloride. Core (rectal) body temperatures were measured at pretreatment and 30, 60, 90, 120, 180, 240 and 300 minutes after treatment. Injection of (+)amphetamine resulted in increased body temperatures in all dose groups excepting males in the low dose (0.005 mM/kg) group after which temperatures returned to and remained at control levels. Injection of (+)alpha-fluoromethylphenylethylamine resulted in initially increased temperatures in all dose groups and at 180 minutes reduced temperatures in high dose males and in medium and high dose females. Hypothermia was not observed after treatment with (+)amphetamine. These results suggest that (+)alpha-fluoromethyl-beta-phenylethylamine has chemical properties distinct from those of (+)-amphetamine.

Amphetamines↗
PubMed1983

Levels of p-tyramine in rat brain after chronic administration of MAO-inhibiting antidepressants.

Groups of male Sprague-Dawley rats were injected acutely or chronically with tranylcypromine (10 mg/kg i.p.) or phenelzine (15 mg/kg i.p.) and extracts of their brains were analyzed by electron-capture gas chromatography for concentrations of p-tyramine. Concentrations of p-tyramine were significantly higher than control levels at all time intervals with both drugs, but these increases showed different patterns with each drug. With tranylcypromine treatment, para-tyramine levels peaked at day 2; with phenelzine treatment they increased steadily over the time course, surpassing levels obtained in tranylcypromine experiments by day 8.

Animals↗
PubMed1983

Stereoisomeric tetrahydro-beta-carbolines differ in their interaction with rat brain benzodiazepine receptors.

A series of (+) and (-) tetrahydro-beta-carboline-3-carboxamide stereoisomers related to the ethyl ester of beta-carboline-3-carboxylate (beta-CCE) have been tested for their ability to displace 3H-flunitrazepam from binding sites prepared from rat cerebral cortex (benzodiazepine receptors). The (+) stereoisomers of ethyl and propyl 1,2,3,4-tetrahydro-beta-carboline-3-carboxamides were the most potent inhibitors of specific 3H-flunitrazepam binding and had significantly lower IC50s than the corresponding (-) isomers. Although the IC50 values for this series of tetrahydro-beta-carboline-3-carboxamides were about 1000 fold higher than the IC50 value for beta-CCE, these compounds were as potent as the beta-carboline alkaloids harmane and harmine. The title compounds may be useful stereoisomeric probes for the characterization of subtypes of specific benzodiazepine binding sites.

Animals↗
PubMed1983

Amphetamine in rat brain after intraperitoneal injection of N-alkylated analogues.

Three N-alkylated analogues of amphetamine were administered intraperitoneally to male Sprague-Dawley rats and whole brain levels of amphetamine (AM) and the N-alkyl analogue were determined one hour after injection of the N-alkylated compounds. The drugs administered were the N-2-cyanoethyl-(I) (fenproporex), the N-3-chloropropyl-(II) (mefenorex) and the N-n-propyl-(III) derivatives of AM: the first two of these are used clinically as anorexiants, and the latter has been used extensively to study aspects of metabolism of AM-like compounds. Analysis of AM, I, II and III was performed using electron-capture gas chromatography with a capillary column after reaction of compounds with pentafluorobenzoyl chloride under aqueous conditions. In a second comparative study, equimolar doses (0.05 mMole/kg) of I or AM were administered intraperitoneally to the rats and brain levels determined after one hour. Results indicate extensive N-dealkylation occurs for compounds I, II and III in the rat.

Amphetamine↗