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)

The effects of 2-phenylethylamine (PEA) and related compounds on the spinal monosynaptic reflex (MSR) were examined using C1-spinalized rats. At low doses, PEA, S(+)-amphetamine, S(+)-methamphetamine and phentermine increased the amplitude of the MSR, whereas high doses of these drugs reduced it. p-Substituted PEA analogs (p-C1-PEA, p-methoxy-PEA and (+/-)-p-C1-amphetamine) only reduced the MSR. Low doses of PEA-related rigid compounds, R(+)-2-aminotetralin, (+/-)-N-methyl-2-aminotetralin and (+/-)-N,N-dimethyl-2-aminotetralin only reduced the MSR. S(-)-2-Aminotetralin did not affect the MSR. Depressions of MSR produced by PEA, S(+)-methamphetamine and R(+)-2-aminotetralin were antagonized by ketanserin and haloperidol which have 5-hydroxytryptamine (5-HT) antagonistic activity, and the MSR depression caused by S(+)-methamphetamine but not PEA and R(+)-2-aminotetralin was abolished by intracisternal 5,6-dihydroxytryptamine treatment or chronic spinal transection. These results suggest that PEA-related compounds cause MSR depression by direct and indirect 5-HT agonistic mechanisms, and support the proposal that the PEA moiety which exists in R(+)-2-aminotetralin is important for the direct 5-HT agonistic activity of some hallucinogens.
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PMID:Structure-activity relationships of phenylethylamine analogs in their serotonergic depressant effects on the spinal monosynaptic reflex in rats. 259 80

Serotonin, or 5-hydroxytryptamine (5-HT), relaxes upper guinea pig stomach, and its possible role as a transmitter in the vagally induced upper gastric adaptive relaxation has been discussed. Such a transmitter is expected to act via other mechanisms than crude muscle depression. To test whether the relaxation response to serotonin is compatible with a putative role as transmitter in gastric adaptive relaxation, we wanted to evaluate whether serotonin acts by crude muscle depression and whether it selectively inhibits histamine or prostaglandin F2 alpha (PGF2 alpha). The study shows that 5-HT, in addition to its relaxatory effect on fundic spontaneous activity, selectively inhibits histamine, whereas PGF2 alpha is not inhibited. It is then concluded that the relaxatory effect of 5-HT is provided through other mechanisms than crude muscle depression and that selective inhibition of intramural agonists, like histamine, is a possible effect mechanism.
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PMID:Serotonin--a possible transmitter for the gastric adaptive relaxation. Interaction with histamine and prostaglandin F2 alpha on pressure responses in the isolated stomach. 259 69

The effects of the 5-hydroxytryptamine-1A (5-HT1A) receptor agonists on the learned helplessness test were investigated. Rats were submitted to a single session of 60 uncontrollable shocks (10-s duration, 1.0 mA, every 60 +/- 40 s) and then treated twice daily with ip injections of either ipsapirone (13 mg/kg daily) or BAY R 1531 (0.375 mg/kg daily) for four consecutive days. On the last day, the animals were submitted to an escape test. The results showed that both drug treatments blocked the deficit in the escape learning (helplessness effect). These data suggest that drugs which stimulate 5-HT1A receptors have an antidepressant-like activity in this animal model of depression.
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PMID:Effects of ipsapirone and BAY R 1531 on learned helplessness. 263 9

The serotonin 5-hydroxytryptamine-1A (5-HT1A) receptor agonists buspirone and gepirone have effects on serotonergic systems, including presynaptic and postsynaptic receptors, that predict both anxiolytic and antidepressant activity. Chronic administration of both drugs produces a down-regulation of 5-HT2 receptors, a finding common to most antidepressant drugs irrespective of mechanism of action. In addition, gepirone induces a full-blown serotonin syndrome in rodents and is active in the behavioral despair test mediated by an action on serotonergic neurons. Buspirone is active in this paradigm when injected directly into the serotonergic dorsal raphe nucleus. The therapeutic effects of both buspirone and gepirone have been assessed in placebo-controlled studies of patients with major depression. Findings in these studies support antidepressant efficacy in addition to anxiolysis. In double-blind studies of patients with major depression treated for 8 weeks, each drug was found to be superior to placebo in improvement in Hamilton Depression and Anxiety total scores as well as individual depressive symptoms. These clinical findings are consistent with preclinical pharmacology suggesting that 5-HT1A partial agonists may possess intrinsic antidepressant activity.
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PMID:Serotonergic anxiolytics and treatment of depression. 265 37

1. The incidence of folic acid deficiency is high in patients with various psychiatric disorders including depression, dementia and schizophrenia. 2. In epileptics on anticonvulsants, folate deficiency often occurs because anticonvulsants inhibit folate absorption. In these patients folate deficiency is often associated with psychiatric symptoms. 3. In medical patients psychiatric symptoms occur more frequently, and in psychiatric patients symptoms are more severe, in those with folate deficiency than in those with normal levels. 4. Many open studies have demonstrated therapeutic effects of folate administration on psychiatric symptoms in folate deficient patients. 5. Several placebo-controlled studies have not demonstrated therapeutic effects, possibly because the doses they used (15-20 mg/day) are known to be toxic and to cause mental symptoms. 6. Two placebo-controlled studies have demonstrated beneficial effects of folic acid administration, one in patients with a syndrome of psychiatric and neuropsychological changes associated with folate deficiency and the other in patients on long-term lithium therapy. In the latter study the dose was only 0.2 mg/day. 7. Folic acid deficiency is known to lower brain S-adenosylmethionine and 5-hydroxytryptamine. S-Adenosylmethionine, which has antidepressant properties, raises brain 5-hydroxytryptamine. Thus, depression associated with folate deficiency is probably related to low brain 5HT. 8. S-Adenosylmethionine is involved in many methylation reactions, including methylation of membrane phospholipids, which influences membrane properties. This may explain the wide variety of symptoms associated with folate deficiency. 9. Because the costs and risks associated with low doses of folic acid (up to 0.5 mg/day) are small, folic acid should be given as an adjunct in the treatment of patients with unipolar or bipolar affective disorders and anorexia, epileptics on anticonvulsants, geriatric patients with mental symptoms and patients with gastrointestinal disorders who exhibit psychiatric symptoms. 10. Although the majority of the patients listed above will probably not be helped by folic acid therapy, a significant minority are likely to have folate-responsive symptoms.
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PMID:Folic acid and psychopathology. 268 87

The actions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT; serotonin) were compared with those of L-3,4-dihydroxyphenylalanine methyl ester (Methyl-L-DOPA) on transmission to spinal interneurones in mid-lumbar (L4 and L5) segments of the cat spinal cord. The drugs were applied ionophoretically and their effects were tested on monosynaptic field potentials evoked by nerve impulses in hindlimb group I and group II muscle afferent fibres and on responses of interneurones with synaptic input from these fibres. Of field potentials recorded at various locations, both NA and 5-HT depressed those evoked from group II fibres in the intermediate and ventral horn regions of the spinal cord but not, or only occasionally, in the dorsal horn. Field potentials of group I origin were not depressed. The tested interneurones were located where group II field potentials were affected. NA, 5-HT and Methyl-L-DOPA depressed responses to electrical stimulation of group II fibres but not responses evoked by group I fibres. The depression consisted of an increase in the latency and a decrease in the number of action potentials evoked by the stimuli. All three drugs were also found to decrease the amplitude of intracellularly recorded monosynaptic EPSPs of group II origin but not of monosynaptic EPSPs evoked in the same neurones by group I fibres. Interneuronal firing induced by DL-homocysteic acid was depressed as effectively as responses to electrical stimulation of peripheral nerves. The possibility of presynaptic and/or postsynaptic mechanisms of the selective depression of synaptic actions of group II origin are discussed.
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PMID:Comparison of effects of monoamines on transmission in spinal pathways from group I and II muscle afferents in the cat. 275 7

We investigated the mode of action of the potent antagonist ICI 170,809 in the 5-hydroxytryptamine (5-HT)2 receptor system of arterial smooth muscle. We used isolated preparations from rat tail artery and calf coronary artery with the endothelium rubbed off. In tail artery ICI 170,809 (0.3-30 nM) antagonized surmountably and nearly competitively the contractile effects of 5-HT (pKB = 10.0) and partially prevented the depression of 5-HT-induced contractions caused by methysergide. Increasing methysergide concentrations gradually prevented the protective effect of ICI 170,809. The combination of 30 nM ICI 170,809 with 300 nM of its demethylated analog ICI 169,369 (pKB = 8.8) caused surmountable blockade of the effects of 5-HT as expected from competition of the three drugs for the same receptor. In calf coronary artery ICI 170,809 (1-100 nM) reduced the maximum contractile response to 5-HT by 35% and caused competitive antagonism (pKB = 10.4) of the remaining 65% of the responses to 5-HT. ICI 169,369 (100 nM) completely prevented the depression of the maximum response to 5-HT caused by ICI 170,809. Methysergide (3 nM) depressed the maximum response to 5-HT by 65 and 30% in the absence and presence of ICI 170,809. The results are consistent with the existence of two interconvertible states R in equilibrium R' of the 5-HT2 receptor. The equilibrium of R in equilibrium R' is shifted toward R' by methysergide greater than ICI 170,809 much greater than ICI 169,369.
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PMID:Dimethylation of the activator ICI 169,369 results in a high-affinity partial deactivator, ICI 170,809, of the arterial 5-hydroxytryptamine2 receptor system. 276 Aug 51

Plasma and urine levels of an endogenous digitalis-like compound (EDLC) are increased in low renin Na+-dependent experimental hypertension, in some normotensive offspring of hypertensive patients and in some essential hypertensive patients. Urine-drived EDLC was purified from 550 L of urine from essential hypertensive patients (n = 8) and from normotensive subjects with a family history of hypertension (n = 27), using flash chromatography on C18 reversed-phase, anion exchange chromatography and various reversed-phase high performance liquid chromatographies. The mechanism of Na+-K+ ATPase inhibition and the related effects of semipurified urine-derived EDLC were studied and compared with those of ouabain. Its action was similar to that of ouabain in 8 out of 10 of the tests applied. The main effects of such a compound were the depression of Na+-K+ pump activity of human erythrocytes, the inhibition of 5-hydroxytryptamine reuptake by human platelets, and the induction of natriuresis in urethanized rats. Therefore, EDLC may be considered as one of the natriuretic hormones whose mechanism of action closely resembles that of ouabain.
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PMID:An endogenous digitalis-like compound extracted from human urine: biochemical and chemical studies. 282 38

Depression of lung endothelial cell metabolic function may be an early and sensitive indicator of lung damage. When such functions are measured in vivo, substrates injected usually must be limited to "trace" doses due to the significant hemodynamic effects of high doses of substrate. Under first-order conditions (i.e., trace doses) the enzyme or transport system rate constant Vmax/Km may be calculated, but independent estimates of each variable (Vmax and Km) are not available. We therefore used multiple indicator-dilution methods and higher substrate concentrations to apply a mathematical model, based on saturable kinetics that yield independent estimates of the apparent kinetic parameters Vmax and Km for pulmonary angiotensin-converting enzyme (ACE). We used the ACE substrate, [3H]benzoyl-phenylalanyl-alanyl-proline ([3H]BPAP) and made these measurements and also estimates of serotonin [5-hydroxytryptamine (5-HT)] removal, before and after acute lung injury induced by intratracheal administration of phorbol myristate acetate (PMA). PMA significantly depressed the percent 5-HT removal (62 +/- 3 to 44 +/- 4%) and BPAP percent metabolism (74 +/- 2 to 66 +/- 2), when trace amounts of either compound were injected as a bolus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary angiotensin-converting enzyme kinetics after acute lung injury in the rabbit. 284 Dec 74

The pharmacological activity of N-[2-(2,6-dimethoxyphenoxy) ethyl]-2-(2-methoxyphenoxy) ethanaminium chloride (ACC-7513) was determined in isolated smooth and cardiac muscle and its effect on blood pressure and heart rate assessed in the spontaneously hypertensive rat (SHR). ACC-7513 was found to be a potent alpha-adrenoceptor blocking agent (pA2:8.33) and a 5-hydroxytryptamine (5-HT) antagonist (pA2:7.01), both in rabbit aortic strips. The affinity for alpha-adrenoceptors was about 20 times greater than that for 5-HT-receptors. High concentrations of ACC-7513 did not block histamine in rabbit aortic strips, or beta 1- or beta 2-adrenoceptor responses induced by isoprenaline in guinea-pig right atria and trachea, respectively, but did block cholinoceptor responses induced by carbachol in rat uterus, non-competitively. High concentrations of ACC-7513 also produced sino-atrial depression in guinea-pig right atria and direct relaxation of depolarized rabbit aortic strips. ACC-7513 depressed blood pressure of conscious SHRs and produced a reflex increase in heart rate. The reductions in pressure were modest and of short duration. It is concluded that: (a) ACC-7513 is a potent, selective alpha-adrenoceptor and 5-HT receptor antagonist; and (b) ACC-7513 is not likely to be useful in the treatment of hypertension.
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PMID:Pharmacological activity of ACC-7513, a selective alpha-adrenoceptor and 5-hydroxytryptamine receptor blocking agent. 286 Sep 40


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