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)

Antipsychotic agents which are considered to depressive to the central nervous system (CNS) but free of dependence liability were used in combination with barbiturates or tranquilizers to study the physical dependence liability in the so-enhanced CNS depression. In the study of physical dependence formation, when CNS depression was maintained in an enhanced stage during the continuous application of the drug combinations, the withdrawal convulsions were enhanced in both frequency and severity. In the crossphysical dependence study, two-drug combinations, i.e., phenobarbital (PhB)-chloropromazine (CPZ), PhB-diphenhydramine (DPH) and nitrazepam-chlorprothixene, and 3-drug combinations (i.e., PhB-CPZ-promethazine and PhB-CPZ-DPH were evaluated. The 2-drug combinations suppressed some of the withdrawal signs, but those at high dosages showed a tendency to aggravate the signs. The 3-drug combinations differed from the 2-drug combinations in that the suppression of withdrawal signs was synergistically enhanced and the barbital withdrawal signs were weak. In conclusion, when CNS depression with PhB was enhanced with combinations of dependence liability-free drugs the drug combinations enhanced withdrawal convulsions both in frequency and severity. The sedation enhanced by the combinations did not always parallel the suppression of barbital withdrawal.
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PMID:Enhancement of drug withdrawal convulsion by combinations of phenobarbital and antipsychotic agents. 611 52

The effects of clomipramine HCl (15 mg kg-1 i.p.) on behaviour, body temperature and brain amines were investigated in rats that had been chronically treated twice daily with increasing doses of delta 9-tetrahydrocannabinol (delta 9-THC, 2-6 mg kg-1 i.v.). delta 9-THC produced a biphasic change in behaviour, stimulation followed by depression, and a pronounced hypothermia. Tolerance developed rapidly to these effects of delta 9-THC. Chronic treatment with delta 9-THC reduced the levels of homovanillic acid, 5-hydroxytryptamine and noradrenaline. The level of dopamine was not altered with chronic treatment and tolerance appeared to develop to the increased levels of 5-hydroxyindoleacetic acid induced by delta 9-THC. Injection of clomipramine, 12-14 h after 2, 5 or 10 days of delta 9-THC treatment induced characteristic changes in the rats behaviour which consisted of writhes, backward kicking, wet shakes, jumps ataxia and front paw and whole body tremor. The severity of the behavioural changes appeared to be dependent on the period of delta 9-THC administration and they were not accompanied by a change in body temperature or consistent changes in brain amines or metabolites. The results indicate that physical dependence on delta 9-THC may occur since clomipramine is able to precipitate changes in behaviour, indicative on an abstinence syndrome, in rats chronically treated with delta 9-THC. It is suggested that tryptaminergic mechanisms are altered during chronic delta 9-THC treatment and that clomipramine induces the behavioural changes by interacting with an altered tryptaminergic system.
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PMID:Time-course of the effects of chronic delta 9-tetrahydrocannabinol on behaviour, body temperature, brain amines and withdrawal-like behaviour in the rat. 612 98

The efficacy of the benzodiazepines in the symptomatic treatment of nonpsychotic anxiety has been well established. Eight benzodiazepines are presently available in the U.S. as anxiolytics. Research conducted over many years has shown that such nonpsychotic anxious patients respond best to anxiolytics if they suffer from high levels of emotional and somatic symptoms of anxiety and from low levels of depression and interpersonal problems. Despite the widespread use of benzodiazepines, it has been difficult to demonstrate tolerance or physical dependence to these drugs when used in therapeutic doses. In addition, data clearly indicate a pattern of conservative benzodiazepine use and possible an under- rather than overuse. Thus, the argument is made that cost-benefit ratios should be considered when discussing the use of benzodiazepines for the treatment of anxiety.
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PMID:Benzodiazepines in the treatment of anxiety. 612 29

The interactions of thyrotropin releasing hormone, its metabolites and synthetic analogues with acute and chronic effects of endogenous and exogenous opiates have been described. The endogenous and exogenous opiates are represented by beta-endorphin and morphine, respectively. The pharmacological effects of opiates include analgesia, temperature effects, respiratory depression, catalepsy, locomotor activity, opiate receptor binding, tolerance, and physical dependence. Thyrotropin releasing hormone and related compounds appear to (a) antagonize hypothermia, respiratory depression, locomotor depression and catalepsy but not the analgesia induced by opiates, (b) inhibit the development of tolerance to the analgesic effect but not to the hypothermic effect of opiates, (c) inhibit the development of physical dependence on opiates as evidenced by the inhibition of development of certain withdrawal symptoms, and (d) suppress the abstinence syndrome in opiate dependent rodents. Thyrotropin releasing hormone does not interact with the opiate receptors in the brain. Potential therapeutic applications of thyrotropin releasing hormone and its synthetic analogues in counteracting some of the undesirable effects of opiates are discussed.
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PMID:Interactions of thyrotropin releasing hormone, its metabolites and analogues with endogenous and exogenous opiates. 614 Nov 21

We relate two cases of amineptine (Survector) overconsumption by patients cured for atypical depression with asthenia and activities deficit as the prevalent symptoms. Prescription of two tablets a day (0,200 g) was respected in one case during six months, and in the other case during two years, with therapeutic benefit on apragmatism. To no obvious reason, within few months both patients had gradually raised the doses to twenty tablets (2 g) and thirty tablets (3 g) respectively: we observed subexcitation, insomnia, sensorial hyperaesthesia, irritability, tachyphemia with dysarthria, anorexia with weight lost of more than 10 kg and amphetamine-like troubles without confusion or delusion, as a result of which both patients were treated for their addiction, in hospital. Treatment with clorazepate perfusions did not cause any physical dependence problems. However, psychological dependence was strong enough for one of the patients to go out, on the third day, against medical decision. As far as we know, in France, only one such case of addiction use at high doses and in single intakes is mentioned in the existing literature. However, our observations suggest that it might be necessary to re-assess the place of amineptine among new antidepressive molecules with psychostimulant abilities.
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PMID:[2 cases of amineptine dependence]. 614 28

Metkephamid is an analog of methionine enkephalin that retains high affinity for the delta receptor and is a systemically active analgesic. Since it is at least 100 times more potent than morphine as an analgesic when placed directly into the lateral ventricles, and is 30 to 100 times more potent on the delta receptor and yet is roughly equipotent on the mu receptor in vitro, it is concluded that it probably produces analgesia by action on delta receptors as well as, or rather than, on mu receptors. It has less tendency to produce respiratory depression, tolerance, and physical dependence than standard analgesics, and it is presently undergoing clinical trial.
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PMID:Metkephamid, a systemically active analog of methionine enkephalin with potent opioid alpha-receptor activity. 625 56

Buspirone HCl (Buspar) is a novel anxiolytic agent unrelated to the benzodiazepines or other psychotherapeutic agents. Animal studies support an anxioselective profile, i.e. relief of anxiety without sedation, muscle relaxation or anticonvulsant activity. Double-blind clinical studies show buspirone to be effective in the treatment of anxiety and anxiety in the presence of depression. The effects of buspirone on psychomotor function, physical dependence and abuse potential tests are similar to those seen with placebo treatments. Mechanism of action studies indicate activity in a variety of neuronal systems.
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PMID:Buspirone: an anxioselective alternative for the management of anxiety disorders. 636 36

Several psychiatric topics have been under recent investigation. Cerebral impairment is now known to occur in over half of alcoholic patients. Its improvement with abstinence and its interference with the considerable intellectual and volitional requirements needed by controlled drinking programmes point to abstinence as the necessary drinking goal when brain damage is suspected. A hereditary element to alcohol dependence has been suggested by several adoption and twin studies, but the many contradictions between research results emphasise that any genetic contribution is overshadowed by socio-cultural factors. Depression and anxiety are frequent accompaniments of alcoholism but are shown by investigations usually as results rather than causes of excessive drinking. The onset of depression with suicidal ideas secondary to alcoholism has been sensitively described, and attention drawn to its identification, potential risk, and prevention. Long-term drug treatments are little used at present, but several developments are feasible. They include an effective long-acting chemical deterrent; drugs to protect against organic damage; sobering agents; immunotherapy; chemical reversal of the neuroadaptive changes responsible for physical dependence; drugs to counteract dysphoria and craving produced by alcohol; pharmacological modification of reflex behaviour; and drugs for the abstinence syndrome and for mood disturbance that are not themselves liable to misuse of dependence. Finally, it is suggested that the syndrome of pathological intoxication is a fictitious state that should be discarded from the descriptive literature.
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PMID:Psychiatric advances in the understanding and treatment of alcohol dependence. 639 77

Cocaine is a powerful euphoriant and it relieves, though only transiently, depression, dread and dysphoria. New patterns of cocaine abuse, such as the inhalation of vaporized cocaine base, the intravenous injection of cocaine hydrochloride and the smoking of coca paste, produce a brief elation that quickly gives way either to a return to the baseline mood or to displeasure, resulting in a strong desire to return to the momentary ecstatic experience, a cycle that leads to compulsive use. The enormous profits made from illicit traffic in cocaine lead to corruption, violence and political destabilization. The individual costs of cocaine abuse include loss of personal fortunes, jobs and families. The safety of cocaine use is a myth. There are a number of ways in which cocaine can be lethal. The high doses of cocaine abused today induce physical dependence, but this is less a contributory factor than the intense psychological craving to perpetuate cocaine use. There is no specific way to treat dysfunctional cocaine use; instead the treatment plan must deal with the individual's specific situation. Except for a reduction of cocaine supply at the source, preventive measures are only feasible in the context of abstinence from all abusable drugs.
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PMID:Recent developments in the abuse of cocaine. 644 Jun 13

3-(3-methyl-3-butenyl)-1,2,3,4,5,6-hexahydro-6, 11-dimethyl-8-hydroxy-2,6-methano-3-benzazocine (KF-1820) is a derivative of benzomorphan and is different from pentazocine only in the site of the double bond. KF-1820 showed potent analgesic activity in all tests performed. KF-1820 was 6 to 12 times and 30 to 40 times more potent than morphine and pentazocine, respectively, when administered subcutaneously. KF-1820 had little or no narcotic antagonist property. Physical dependence liability tests indicated that KF-1820 may be a little less, or as liable as, pentazocine to produce physical dependence. ID50 values of KF-1820, pentazocine and morphine for depression of contractions of isolated guinea pig ileum to coaxial stimulation correlated well with their analgesic activities in the rodent. The dissociation equilibrium constant of KP-1820 confirmed the in vivo finding that KF-1820 had little or no narcotic antagonist property.
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PMID:Pharmacological studies of 3-(3-methyl-3-butenyl)-1,2,3,4,5,6-hexahydro-6,11-dimethyl-8-hydroxy-2,6-methano-3-benzazocine. 645 8


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