Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new benzamide, cis-N-(1-benzyl-2-methylpyrrolidin - 3 - yl) - 5 - chloro - 2 - methoxy - 4 - methylaminobenzamide (YM-09151-2) exhibited more potent and longer-lasting inhibitory effects on apomorphine-induced behaviours (stereotyped behaviour, emesis and hypothermia), and methamphetamine-induced stereotyped behaviour, conditioned avoidance response and open field behaviour, conditioned avoidance response and open field behaviour than either structurally similar benzamides (YM-0850 and sulpiride) or classical neuroleptics [chlorpromazine (CPZ) and haloperidol(HPD)]. Such inhibitory effects of YM-09151-2 relative to cataleptogenicity were greater than those of CPz and HPD. In contrast, sulpiride elicited few of the neuroleptic effects described above. YM-09151-2, a potent inhibitor for dopamine-sensitive adenylate cyclase (Ki: 3.0 nM) reduced, in a selective manner, the binding of [3H]dopamine to the dopamine D1 receptor (Ki:4.8 nm) associated with adenylate cyclase rather than to the dopamine D2 receptor (Ki: 0.98 microM) independent of adenylate cyclase. Sulpiride, on the contrary, inhibited only the binding to the dopamine D2 receptor, CPZ and HPD antagonized [3H]dopamine nonselectively at the two distinct dopaminergic receptors. These results suggest that YM-09151-2 is a potent and long-lasting neuroleptic with a highly selective blocking action on the dopamine D1 receptor.
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PMID:Neuroleptic properties of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) with selective antidopaminergic activity. 611 70

SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol) possesses pharmacologic effects similar to standard antipsychotics, including selective supression of conditioned avoidance responding in rats and squirrel monkeys, blockade of apomorphine-induced stereotypy in rats and blockade of methamphetamine-induced lethality in aggregated mice. At effective doses in these tests, no changes in gross behavior, neurological or autonomic function were observed. In contrast to the standards tested, SCH 23390 blocked dopamine-stimulated adenylate cyclase at concentrations (IC50 = 0.01 microM) about 2000 times lower than those needed to block spiperone binding (IC50 = 24 microM). This suggests specific D1-receptor antagonism. Inability of SCH 23390 to cause hyperprolactinemia, considered to be a D2-receptor effect, is consistent with this hypothesis. SCH 23390 showed lower increases in dopamine turnover suggesting that the blockade of SCH 23390 may be more specific for post- than presynaptic sites. Additional evidence for the selectivity of SCH 23390 among putative postsynaptic dopamine sites includes its lack of effect on apomorphine-induced hypothermia or emesis. Based on these results, it is postulated that SCH 23390 is a selective D1-receptor antagonist.
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PMID:SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems. 613 95

The (+)-enantiomer of 1,2,3,4a,5,6-hexahydro-9-hydroxy-4-n-propyl-4H-naphth[1,2-b][ 1,4]-oxazine [(+)-PHNO] is demonstrated to be a potent and direct dopamine (DA) agonist in several in vivo and in vitro test procedures. In vitro (+)-PHNO inhibited binding of [3H]apomorphine (IC50 = 23 nM) or [3H]spiperone (IC50 = 55 nM) to rat striatal membranes. Because (+)-PHNO failed to stimulate adenylate cyclase in carp retina, it was classified as a D-2 agonist. ED50 values (shown in parentheses) derived in DA receptor-related in vivo tests were as follows: in mice, (+)-PHNO produced hypothermia (13 micrograms/kg i.p.) and postural asymmetry in the unilaterally caudectomized animal (4 micrograms/kg i.p.). In the rat, (+)-PHNO produced stereotypy (10 micrograms/kg i.p.) and contralateral turning in 6-hydroxydopamine-lesioned animals (5 micrograms/kg i.p.) that lasted 1 to 3 hr. Whereas both of the latter effects were blocked by haloperidol, prior treatment with depletors of endogenous catecholamines, reserpine or alpha-methylparatyrosine failed to reduce (+)-PHNO-induced stereotypy. The naphthoxazine also produced emesis in beagles (0.05 micrograms/kg i.v.) that was blocked by L-646,462, a peripherally selective DA receptor antagonist. (+)-PHNO was well absorbed when given p.o., producing contralateral turning (10 micrograms/kg) with a ratio of p.o. to i.p. ED50 values of 2. This ratio was much lower than those derived for n-propylnorapomorphine (60) and apomorphine (54). At the DA autoreceptor, (+)-PHNO inhibited the accumulation of dOPA in the gamma-butyrolactone-treated rat (11 micrograms/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacologic profile of a novel potent direct-acting dopamine agonist, (+)-4-propyl-9-hydroxynaphthoxazine [(+)-PHNO]. 643

Snake bite was diagnosed in 125 dogs and 115 cats over 10 years. Young sporting dogs and young cats were mainly affected. More dogs (48%) were seen in contact with tiger snakes than cats (7%). One hundred and four (84%) dogs and 89 (76%) cats were bitten in the warmer months of the year (October to March). As the incidence rose in September/October, dogs were bitten on days when the temperature was near 20 degrees C or over. The commonest presenting signs were dilated pupils and absences of pupillary light reflex. Dyspnoea, hypothermia, hindleg ataxia and glycosuria were common features in cats. Vomiting, tachypnoea, hyperthermia and complete flaccid paralysis were often seen in dogs. The overall recovery rate after administering antivenene was 90% for cats and 83% for dogs. Death from anaphylaxis as a result of giving antivenene occurred in 3 cats and one dog. Dogs treated soon after being bitten recovered more rapidly. There was no correlation between the bite-to-treatment period and the treatment-to-recovery period for cats.
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PMID:Clinical features therapy and epidemiology of tiger snake bite in dogs and cats. 649 4

The effects of body temperature and behavior of 2,4-dinitrophenol injected into the cerebral ventricles of the cat was investigated in these experiments. Infused in a volume of 0.1-0.2 ml, 2,4-dinitrophenol produced a dose-dependent fall in body temperature, the duration of which was also dose-dependent. Apart from hypothermia, 2,4-dinitrophenol evoked mydriasis, respiratory irregularities, urination, vomiting, ataxia, muscular weakness, sedation and occasional clonic-tonic convulsions. Of all the autonomic effects, the most consistent was the effect on thermoregulation. The possible mechanisms of action in the brain of 2,4-dinitrophenol on the thermoregulatory mechanisms are discussed.
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PMID:Hypothermic effect of 2,4-dinitrophenol infused ICV in the cat. 649 41

Clinicopathologic findings were retrospectively evaluated in 26 cats and 24 dogs with ethylene glycol intoxication. Common clinical signs were ataxia, depression, vomiting, and hypothermia. Characteristic alterations in the hemogram and serum chemical profile included neutrophilia, lymphopenia, azotemia, hyperphosphatemia, hypocalcemia, hyperglycemia, and decreased whole blood bicarbonate. Common urinalysis findings included isosthenuria, proteinuria, glucosuria, hematuria, calcium oxalate and hippurate crystalluria, and the presence of renal epithelial cells, white blood cells, and granular and cellular casts in the urine sediment. The high death rate (78%) was attributed to delays in presentation, diagnosis, and therapy.
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PMID:Clinicopathologic findings in dogs and cats with ethylene glycol intoxication. 669 34

A case of Wernicke's encephalopathy with ataxia, confusion, memory loss, partial seizures of complex behavior and hypothermia, subsequent to thiamine depletion due to chronic malnourishment and triggered by an episode of acute vomiting and diarrhea, is reported, Computerized tomography (CT-scan) depicted small bilateral lesions in areas adjacent to the walls of the third ventricle, common location of the lesions seen in autopsy material of Wernicke's encephalopathy. Early diagnosis and treatment with vitamin B complex supplemented with intensive mnemonic and cognitive therapy led to complete recovery in a ten day period.
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PMID:Wernicke's encephalopathy. A case report with neurophysiologic and CT-scan studies. 686 52

The toxicology of a potentially useful antitumor agent, 2,4-diamino-5-adamantyl-6-methylpyrimidine (DAMP), and its ethanesulfonate salt has been studied in beagle dogs after 1 to 20 doses. Two types of toxicity could be discerned: the acute central nervous system toxicity manifested by vomiting, convulsions, and minor hypothermia; and the antiproliferative toxicity, similar to that of other folate antagonists, manifested by diarrhea, anorexia, loss of body weight, and hematological changes as well as changes in blood chemistry. There is evidence of a cumulative effect of the drug with respect to antiproliferative toxicity. Characteristically, the animals could be protected against the antiproliferative toxicity by simultaneous administration of folinic acid. The pharmacokinetics of the ethanesulfonate salt of DAMP was studied after i.v. administration of sublethal doses (5 mg/kg) of tritium-labeled drug. Sixty-three % of the administered dose was excreted in the urine and 10% was excreted in the feces within 48 hr after drug administration. Thus, about 27% of the drug was not recovered, and it is possible that it persists in the tissues for a period of several days. Analysis of the plasma and urine revealed that DAMP was metabolized rapidly. At least 2 metabolites were found in plasma and urine, one lipophilic and one hydrophilic, the latter being the predominant form. Pharmacokinetic data were successfully fitted to a model consisting of central and peripheral DAMP compartments and a DAMP metabolite compartment. DAMP was very rapidly sequestered in the peripheral compartment with a rapid phase half-life of 23 sec. The slower phase of DAMP plasma disappearance had a half-life of 3 hr. The short plasma half-life and rapid metabolism distinguished this drug from other lipophilic antifolates.
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PMID:Toxicity and pharmacokinetics of a new antifolate, 2,4-diamino-5-adamantyl-6-methylpyrimidine, in dogs. 707 98

Nicotine produced a distinct reproducible syndrome in the conscious dog when injected intravenously or intracerebroventricularly. Intravenously administered nicotine (40 micrograms/kg/min for 20 minutes) increased cardiac and respiratory rates and produced analgesia, miosis, hypothermia, behavioral restlessness and emesis. When microinjected into the third cerebral ventricle, nicotine (100-200 micrograms) similarly increased cardiac and respiratory rates and pupillary diameter; and produced behavioral restlessness, emesis, erratic analgesia and maintained wakefulness and a desynchronized EEG. Microinjection of nicotine (5-25 micrograms) into the periaqueductal gray failed to alter any of the parameters studied. Intravenous pretreatment with the opioid antagonist naltrexone (2 mg/kg) influenced the action of intravenous nicotine on certain physiological systems. While naltrexone alone produced a significant degree of tachycardia, miosis, and analgesia, it potentiated the tachypnea and antagonized the miotic response evoked by nicotine. Methionine-enkephalin was detected in perfusates obtained from the lateral cerebral ventricles of conscious dogs. Nicotine produced a non-significant decrease in enkephalin levels. These observations suggest that there are interactions between endogenous opioid and nicotinic processes. However, they are complex and may differ from one functional system to another.
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PMID:Interaction between nicotine and endogenous opioid mechanisms in the unanesthetized dog. 717 83

Aziridinylbenzoquinone (AZQ: NSC-182986), is a quinone derivative which has been shown to have activity in implanted murine tumor systems. Toxicity in small and large animals included hypothermia, diarrhea, anorexia, emesis, weight loss, and gastrointestinal bleeding. In addition, there was myelosuppression and elevated liver function tests. In a phase I study at the Mayo Clinic, dose-limiting toxicity was myelosuppression. Patients with prior radiation therapy or prior chemotherapy were more sensitive to this toxicity. A dose schedule of 27.5 mg/m2 q4 weeks was recommended for patients who had had no previous chemotherapy and 22.5 mg/m2 for previously treated patients or for patients who had had extensive prior radiation therapy. The objective of this study was to determine therapeutic activity for AZQ in patients with advanced colorectal adenocarcinoma.
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PMID:A phase II study of aziridinylbenzoquinone (AZQ) in advanced large bowel carcinoma. 718 Aug 32


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