Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although a receptor exists for cannabinoid drugs, it is uncertain which pharmacological actions this receptor mediates. This structure-activity relationship investigation was initiated to determine which effects might correspond to binding affinity for the cannabinoid receptor, as well as to explore the binding requirements of this site. The ability of nearly 60 cannabinoids to displace [3H]CP-55,940 [(-)-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-4-[3-hydroxy propyl] cyclohexan-1-ol] was determined before establishing correlations between receptor affinity and in vivo pharmacological potency. Analysis of [3H]CP-55,940 binding indicated a Hill coefficient of 0.97, a Bmax of 499 pM (3.3 pmol/mg of protein) and an apparent Kd of 924 pM. Closer inspection indicated the binding assay exhibited "zone B" characteristics, and use of correction equations indicated a true Kd for CP-55,940 of 675 pM. The structure-activity relationship indicated the importance of side chain structure to high-affinity binding, with the most potent analogs (K1 < 10 nM) possessing either a dimethylheptyl side-chain, a similarly complex branched side chain or a halogen substituent at the 5' position. Comparative analysis of K1 values to in vivo potency in a mouse model indicated a high degree of correlation between parameters for the depression of spontaneous locomotor activity (r = 0.91) and for the production of antinociception (r = 0.90), hypothermia (r = 0.89) and catalepsy (r = 0.85). Similarly high correlations were demonstrated between binding affinity and in vivo potency in both the rat drug discrimination model (r = 0.81) and for psychotomimetic activity in humans (r = 0.88).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities. 847 8

Aspects of psychiatric emergencies of special interest to the general physician are discussed. The perception that a problem constitutes an emergency is often subjective and sometimes reflects the anxieties of others rather than a real need for urgent treatment. Keeping calm and unhurried in front of an agitated patient might be as important as the use of a neuroleptic. The rather unusual psychopathological phenomena catalepsy and psychogenic twilight state (psychogenic trance) are mentioned in view of their importance for urgent assessment of mental status. The scope of the problem of suicide is outlined as far as the general physician is involved. Special attention is paid to panic disorder and attacks, a relatively new concept in medicine. Since the symptoms mimic those of cardiac, endocrine and convulsive disorders, patients with such symptoms often come to the attention of general physicians and frequently use the services of emergency departments. Early identification and treatment of panic disorder might help to avoid unnecessary repeated emergency department visits, and at the same time reduce the associated high risk of suicide and other psychiatric disorders such as depression as well as drug and alcohol abuse.
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PMID:[Emergency: the internist as psychiatrist]. 848 84

Withdrawal from chronic use of psychostimulant drugs in humans induces a clinical syndrome characterized by fatigue, psychomotor depression, anhedonia, and disturbances of sleep. Spontaneous locomotor activity and catalepsy were assessed in rats during withdrawal from a schedule of intravenous self-administration of high doses of amphetamine. At 2 and 4 days after cessation of amphetamine self-administration, rats showed a state of psychomotor retardation as measured by reduction of locomotor activity and increased catalepsy. In search of a possible pharmacologic means of intervention for such behavioral changes, the effect of repeated treatment with the nonaddictive ergot derivative lisuride during the withdrawal phase was evaluated. At a dose devoid of any effects on locomotor activity, lisuride completely prevented the reduction in locomotor activity and the increase in catalepsy produced by amphetamine withdrawal. These results suggest the need for further studies on lisuride as a possible novel treatment during withdrawal from psychostimulant drugs in humans.
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PMID:Lisuride reduces psychomotor retardation during withdrawal from chronic intravenous amphetamine self-administration in rats. 850 48

In an attempt to elucidate the physiological basis of hypnosis, we investigated the changes of whole-brain and regional cerebral glucose metabolism, from a state of resting wakefulness to a hypnotized state with whole-body catalepsy, using positron emission tomography and the 2[18F]fluorodeoxyglucose method in 15 highly hypnotizable adults. Neither the random order of study conditions nor any of the other experimental factors had a measurable effect, and there was no statistically significant global activation or metabolic depression. However, repeated measures analysis of variance revealed a statistically significant heterogeneity of symmetric regional responses: Mainly the occipital areas, including visual and paravisual cortex, became relatively deactivated, while some metabolic recruitment was found in structures involved in sensorimotor functions. The observed pattern of changes of regional cerebral activity corresponds with the shift of attention away from normal sensory input that hypnosis is known to produce.
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PMID:Hypnotic catalepsy-induced changes of regional cerebral glucose metabolism. 854 1

Recent breakthroughs in cannabinoid research, including the identification of two cannabinoid receptors (CB receptors) and a family of endogenous ligands, the anandamides, may shed new light on the sequelae of pre- and perinatal exposure to cannabinoid receptor ligands and enable the experimental manipulation of the endogenous ligand in the developing organism. In the present study we examined the behavioural response to anandamide (ANA) in developing mice from day 13 into adulthood. We observed that depression of ambulation in an open field and the analgetic response to ANA are not fully developed until adulthood. In a separate set of experiments, we administered five daily injections of ANA (SC, 20 mg/kg) during the last trimester of pregnancy. No effects on birth weight, litter size, sex ratio and eye opening were detected after maternal ANA treatment. Further, no effects on open field performance of the offspring were observed until 4 weeks of age. However, from 40 days of age, a number of differences between the prenatal ANA and control offspring were detected. Thus, the offspring from ANA-treated dams showed impaired responsiveness to a challenge with ANA or delta 0-THC expressed as a lack of immobility in the ring test for catalepsy, hypothermia and analgesia. On the other hand, without challenge, they exhibited a spontaneous decrease in open field activity, catalepsy, hypothermia and a hypoalgetic tendency. These data suggest that exposure to excessive amounts of ANA during gestation alters the functioning of the ANA-CB receptor system. Further experiments investigating responsivity of the immune system suggest an increased inflammatory response to arachidonic acid, and enhanced hypothermic response to lipopolysaccharide in prenatally treated offspring. The results are discussed in relation to other manipulations of the maternal milieu, especially prenatal stress. It is concluded that alterations induced by prenatal exposure to ANA, cannabinoids and other psychotropic drugs or prenatal stress, share common features, but the data also suggest specific effects on the ANA-CB receptor system.
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PMID:Developmental aspects of anandamide: ontogeny of response and prenatal exposure. 877 60

Several fentanyl analogs (Bagley et al., 1989, J. Med. Chem. 32, 663) were compared to fentanyl and morphine for their effects on respiratory depression as determined by arterial blood gas (pH, pCO2 and pO2) measurements. Fentanyl (0.1 mg/kg), morphine (10 mg/kg), #16 (1-phenethyl-4-[N-(pyridin-2-yl)-N-(methoxymethylcarbonyl)amino] piperidine, 1 mg/kg), #17 (1-phenethyl-4-[N-(pyridin-2-yl) -N-(2-furoyl)amino]piperidine, 0.5 mg/kg) and #29 (1-phenethyl-4-[N- (pyrimidin-2-yl)-N-(methoxy-methylcarbonyl) amino]piperidine, 10 mg/kg) produced significant respiratory depression in rats. Pretreatment with the mu1-opioid receptor selective antagonist, naloxonazine (10 mg/kg), blocked the respiratory effect of fentanyl and its analogs, but not that of morphine. The results suggest that the mu1-opioid receptor plays an important role in the respiratory effects of fentanyl and its analogs. Hence, the mechanism of fentanyl-induced respiratory depression appears to be distinct from that produced by morphine. The most likely explanation for this difference is the possible contribution of muscle rigidity and catalepsy to the observed changes in blood gas parameters caused by the fentanyl analogs, while the respiratory depression of morphine, measured by these same parameters, appears to be independent of its effect on muscle rigidity.
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PMID:Evidence for mu1-opioid receptor involvement in fentanyl-mediated respiratory depression. 889 2

We investigated the differences between the action of haloperidol and pimozide on dopamine metabolism and on catalepsy in periods up to 6 weeks after cessation of chronic administration of the neuroleptics to male Wistar rats. Dopamine and its metabolites (dihydroxyphenylacetic and homovanillic acids) were measured, using high-performance liquid chromatography (HPLC), in the frontal cortex, nucleus accumbens, and striatum. Both neuroleptics produced similar effects after a single dose: catalepsy and an increase of dopamine metabolism in the brain structures. However, haloperidol and pimozide differed after chronic treatment. In haloperidol-treated rats hypersensitivity of the dopaminergic system developed at the end of 2 weeks' administration, as evidenced by depression of dopamine metabolism. The biochemical changes were accompanied by behavioral hyperactivity that lasted up to 3 weeks. Dopamine metabolism in rats treated with pimozide was normal from 24 h after the end of the treatment, while catalepsy was maintained at the high level for up to 8 days and was observable up to 3 weeks after the last dose. Our results suggest that in contrast to haloperidol, pimozide is not able to produce adaptive changes leading to supersensitivity of the dopaminergic system. This may be the consequence of its potent Ca2+ channel blocking action.
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PMID:Different effects of chronic administration of haloperidol and pimozide on dopamine metabolism in the rat brain. 891 13

Epiphysisectomy was shown to increase depression in swimming rats, whereas epiphysisectomy combined with blending decreased it. Epiphysisectomy alone affected the minute rhythms of haloperidol catalepsy while the combined action was less obvious.
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PMID:[The effect of the blinding of rats on the dynamics of short-period rhythmic processes with removal of the epiphysis]. 896 43

The objective of the present study was to determine the neurobehavioral effects of the putative endogenous cannabinoid ligand, anandamide, and its influence on cannabinoid (CB1) receptor gene expression. The effect of acute administration of anandamide to C57BL/6, DBA/2, and ICR mice were evaluated in motor function and emotionality tests. The C57BL/6 and ICR mouse strains were more sensitive than the DBA/2 strain to the depression of locomotor activity and stereotyped behavior caused by anandamide. Although anandamide produced catalepsy in all three strains, anandamide induced ataxia in the minus-maze test only in the C57BL/6 animals and only at the lowest dose used. In the plus-maze test system, anandamide produced a mild aversive response, and by the third day of treatment the mouse strains developed an intense aversion to the open arms of the plus-maze. Northern analysis data using the recently cloned mouse cannabinoid receptor cDNA as a probe indicated that there was abundant expression of CB1 gene in the whole brain of the ICR mouse than in the brains of the C57BL/6 and DBA/2 strains with or without pretreatment with anandamide. The anandamide induced neurobehavioral profile does not seem to correspond to the CB1 gene expression in the mouse strains. It is, therefore, unlikely that the CB1 receptor mediates all the cannabinomimetic effects of anandamide in the brain.
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PMID:Neurobehavioral effects of anandamide and cannabinoid receptor gene expression in mice. 943 4

Incidence of severe depression is very common in Parkinson's disease (PD). Use of antidepressants in such cases is known to improve or worsen the existing PD. However, prediction of the effect of antidepressant on symptoms of PD is limited due to lack of suitable animal model. The present study examines the possibility of using haloperidol-induced catalepsy model in rats for this purpose. Antidepressants showed distinct effect on haloperidol-induced catalepsy, although most of them reduced forced-swimming induced immobility. In general, antidepressants with greater noradrenergic reuptake inhibition (desipramine, imipramine, amitriptyline, nortriptyline, protriptyline and maprotiline) reduced, whereas those with serotonergic reuptake inhibition (fluoxetine and clomipramine) increased haloperidol-induced catalepsy. Mianserin, an atypical antidepressant, and alprazolam, a benzodiazepine receptor analogue had no effect on haloperidol-induced catalepsy. The results suggest that haloperidol-induced catalepsy model in rats needs to be incorporated in the screening procedure when evaluating the utility of antidepressant drugs for the treatment of depression associated with PD.
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PMID:Haloperidol-induced catalepsy: a model for screening antidepressants effective in treatment of depression with Parkinson's disease. 956 63


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