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 actions of various doses of haloperidol, pimozide, clozapine, and phenoxybenzamine were assessed on a conditioned-avoidance response (CAR) in control and 6-hydroxydopamine-treated rats, using a pole-climbing device. Haloperidol proved to be the most potent in disrupting the CAR. Pimozide was about 1.6 times less potent, and clozapine and phenoxybenzamine were approximately 52 and 155 times less potent than haloperidol, respectively. Prior treatment with 6-hydroxydopamine slightly enhanced the sensitivity to some of the doses of the DA and NE antagonists. Significantly lower levels of responding, however, were observed only after the highest dose of primozide. Clonidine was not only ineffective in reverting avoidance decrements, but also induced a further decline of the CAR. Apomorphine produced a partial, but significant, reversal of the haloperidol and pimozide-induced depression of conditioned responses. Regarding the clozapine-pretreated animals, a significant antagonism was observed only with the smaller dose of apomorphine. The highest dose induced a further decline of the CAR. The DA agonist was also ineffective in the phenoxybenzamine-injected rats. Amphetamine was effective in antagonizing the avoidance decrements produced by all the CA antagonists. Our results support the suggestion that CAR depends on both DA and NE mechanisms. DA seems to be more significant that NE, however, since the CAR was more depressed when receptors depending on the former neurotransmitter were blocked.
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PMID:The actions of dopaminergic and noradrenergic antagonists on conditioned avoidance responses in intact and 6-hydroxydopamine-treated rats. 10 52

1. The effects of dopamine, its analogues and antagonists on the chemosensory discharges originating from carotid bodies in situ were studied in anaesthetized cats. 2. Intracarotid (I.C.) injections of 100 ng or more of dopamine produced transient depression of the frequency of carotid nerve chemosensory discharges. Short term (1-5 sec) complete inhibition was usually elicited by 2 microgram dopamine. 3. I.V. injections of dopamine also produced inhibition of chemosensory discharges, an effect observed with doses which were still too low to produce changes in systemic arterial pressure. Half-maximal inhibition (ID50) of chemoreceptors was elicited with a mean dose of 84 ng.kg-1. 4. I.C. and I.V. injections of apomorphine and amantadine also produced transient inhibition of chemosensory activity. Higher doses of these analogues of dopamine were needed to produce this effect, and the resulting inhibition usually did not silence the nerve discharges. Apomorphine inhibition was slightly more prolonged than that with dopamine. 5. Large doses of amphetamine and tyramine, inducers of dopamine release, did not produce inhibition of chemosensory discharges. 6. The effects of two classes of dopamine antagonists were tested. Dose-response curves for dopamine and apomorphine inhibition were displaced to the right by administration of phenothiazines (chlorpromazine and perphenazine) and butyrophenones (haloperidol and spiroperidol). In animals treated with perphenazine or spiroperidol, dopamine became a stimulator of chemoreceptor activity. 7. It is suggested that dopamine present in carotid body may operate as a modulator of chemosensory activity.
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PMID:Effects of dopamine analogues and antagonists on carotid body chemosensors in situ. 62 5

Three different syndromes produced by congeners of morphine have been identified in the nondependent chronic spinal dog. These syndromes have been attributed to interaction of agonists with three distinguishable receptors (mu, kappa and sigma). Morphine is the prototype agonist for the mu receptor, ketocyclazocine for the kappa receptor and SKF-10,047 for the sigma receptor. The morphine syndrome (mu) in the dog is characterized by miosis, bradycardia, hypothermia, a general depression of the nociceptive responses and indifference to environmental stimuli. Ketocyclazocine (kappa) constricts pupils, depresses the flexor reflex and produces sedation but does not markedly alter pulse rate or the skin twitch reflex. SKF-10,047 (sigma), in contrast to morphine and ketocyclazocine, causes mydriasis, tachypnea, tachycardia and mania. The effects of these three drugs can be antagonized by the pure antagonist naltrexone, indicating that they are agonists. Further, chronic administration of morphine, ketocyclazocine and SKF-10,047 induces tolerance to their agonistic effects. Morphine suppresses abstinence in morphine-dependent dogs while ketocyclazocine does not. Ketocyclazocine at best precipitated only a liminal abstinence syndrome in the morphine-dependent dog, indicating that it had little affinity for the morphine receptor. Ketocyclazocine thus appears to be a selective agonist at the kappa receptor. Further, it has been shown that buprenorphine is a partial agonist of the mu type which both suppressed and precipitated abstinence in the morphine-dependent dog while morphine and propoxyphene are stronger agonists. Apomorphine and SKF-10,047 produce similar pharmacologic effects suggesting that sigma activity may involve a dopaminergic mechanism.
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PMID:The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. 94 47

Microinjections of apomorphine (25-300 mug) were made into the lateral ventricle, dorsal nucleus of the vagus and ventromedial nucleus of the hypothalamus of cats through a stereotaxically implanted cannula-electrode. Apomorphine caused depressor and bradycardic effects without any dose-response relationship. At the above doses of apomorphine the efferent vagal discharges werr markedly increased concurrent with cardiovascular changes. Respiration was not affected except at higher doses causing depression in some experiments. Pretreatment with atropine, scopolamine or haloperidol abolished those responses. Similar results were observed with bivagotomy and midcollicular transection. Dopamine (125-100 mug), acetylcholine (10-100 mug) and norepinephrine (25-100 mug) caused similar cardiovascular changes, as in the case of apomorphine, and such effects were blocked by both specific and non-specific autonomic blackers. Thus the hypothalamus and the dorsal nucleus of the vagus appear to be inbolved in the central cardiovascular effects of apomorphine and such effects may be mediated through more than one neurotransmitter mechanisms.
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PMID:Cardiovascular effects of central microinjections of apomorphin in cats. 109 98

The effects of some drugs on apomorphine-induced stereotyped behavior were studied in male cynomolgus monkeys. Apomorphine produced the dose-dependent stereotyped behavior characterized mainly by continuous licking and biting, and repetitive movements of the hands, head and body in the monkeys. Penfluridol as well as haloperidol showed a clear antagonistic effect on the apomorphine-induced stereotyped behavior, while chlorpromazine was less antagonistic than haloperidol. The antagonistic effect of penfluridol lasted longer than that of haloperidol. Reserpine did not inhibit the apomorphine-induced stereotyped behavior though the drug elicited markedly the behavioral depression and alpha-methyl-p-tyrosine also did not block the stereotyped behavior. Nialamide did not depress the apomorphine-induced stereotyped behavior. In provoking the stereotyped behavior in monkeys, apomorphine probably acts directly on dopamine receptors in the extrapyramidal system, and penfluridol is suggested to act as a dopamine receptor blocker with a long action. The results indicate that protection against apomorphine-induced stereotyped behavior in monkeys may be a useful method for evaluating neuroleptic drugs.
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PMID:Effects of penfluridol and other drugs on apomorphine-induced stereotyped behavior in monkeys. 117 Oct 14

In order to examine the effect of chronic neuroleptics on spinal dopaminergic system, rats were treated with haloperidol (0.5 mg/kg IP) for 21 days and the monosynaptic mass reflex (MMR) as well as dopamine (DA) metabolism were investigated. MMR, recorded from ventral root L6 following supramaximal stimulation to ipsilateral dorsal root L6 in spinalized rats, were found to be unaffected following chronic haloperidol treatment when compared to control. Apomorphine (0.1 mg/kg IV) caused 10-20% depression of MMR in control animals which was augmented to 40-50% in chronically haloperidol-treated animals suggesting an upregulation of DA receptors in the spinal cord. DA content of lumbar region of the spinal cord was unaffected whereas its major metabolite, homovanillic acid, was significantly reduced in chronic haloperidol-treated animals. This decreased utilization of DA may compensate the upregulation of DA receptors to maintain the physiological homeostasis of the spinal dopaminergic system.
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PMID:Supersensitivity of spinal dopaminergic receptors in rat after chronic haloperidol. 154 Aug 40

Effects of the dopamine (DA) D1 antagonist SCH 23390 and the DA D2 antagonist (-)-sulpiride on apomorphine-induced characteristic changes in spontaneous motor activity were investigated in mice using the system we have devised for automatically analyzing animal behaviors in mice. Apomorphine (3 mg/kg, SC) markedly increased parameters of spontaneous motor activity such as locomotor activity and rearing time. Apomorphine-induced increase in locomotor activity had peaks at 5-20 and 30-50 min after administration, and its trough was closely related to the marked increase in rearing time induced by this agonist. Apomorphine-induced locomotor activity accumulated over a 40-min period from 5 to 45 min after apomorphine injection, during which apomorphine-induced increase in rearing time peaked, was significantly increased by intraperitoneal administration of 0.03 and 0.1 but not 0.01 mg/kg SCH 23390. Apomorphine-induced increase in rearing time was dose-dependently depressed by this antagonist. In contrast, (-)-sulpiride (10-40 mg/kg, IP) decreased apomorphine-induced increases in rearing time and locomotor activity rather than enhancing the latter parameter. These data suggest that the apparent enhancement by SCH 23390 of apomorphine-induced locomotor activity is mediated through DA D1 receptors and does not always correlate with depression of apomorphine-induced rearing behavior in mice.
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PMID:Apparent enhancement by SCH 23390 of apomorphine-induced locomotor activity in mice. 178 98

U-66444B was evaluated for pre- and postsynaptic effects in dopaminergic (DA) cell body and nerve terminal regions of chloral hydrate anesthetized rats. U-66444B depressed DA neurons in substantia nigra pars compacta and ventral tegmental area with a potency three times that for apomorphine. With a sufficient dose, cells were completely silenced. Activity was found to reside principally in the (+)-stereoisomer, U-68553B. The effects of U-66444B and U-68553B were reversed by 0.1 mg/kg haloperidol. Apomorphine, but not U-66444B nor U-68553B, depressions were accompanied by rapid tachyphylaxis. After 2 wk of U-66444B 0.6 mg/kg/day, potency was not significantly affected. By using in vivo voltammetry, 100 micrograms/kg U-68553B produced a depression in DA release that was more dramatic and more prolonged than that for 500 micrograms/kg apomorphine. On DA postsynaptic receptors, iontophoretic U-66444B and apomorphine were approximately equipotent in depressing caudate neuron firing. It is concluded that U-66444B and its active enantiomer, U-68553B, are more potent, longer acting and possibly more selective as DA autoreceptor agonists than apomorphine. The propensity to produce tolerance appears weak.
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PMID:U-66444B and U-68553B, potent autoreceptor agonists at dopaminergic cell bodies and terminals. 197 31

This review examines the various clinical options used to elicit gastric emptying, viz. drug-induced emesis, mechanical pharyngeal stimulation, gastric lavage, and catharsis. Apomorphine and syrup of ipecac are the 2 drugs most frequently used for induction of emesis. Both agents act centrally and, in addition, syrup of ipecac has a peripheral action. Toxins ingested or foods previously eaten may inhibit or enhance emetic action by interfering with mediating and conducting mechanisms. Studies indicate that both syrup of ipecac and apomorphine are similarly effective in inducing emesis; however, apomorphine has a shorter reaction time compared with syrup of ipecac. There are more risks involved with the use of apomorphine, since it causes central nervous system and respiratory depression. Syrup of ipecac has been shown to be relatively safe when used in its recommended dosage for emesis. However, several toxicities have been reported with the use of the fluid extract of ipecac. Emesis is contraindicated in patients who are obtunded or comatose, and in patients who have ingested stimulants, some hydrocarbons, or corrosives. Mechanical pharyngeal stimulation is a simple method of inducing emesis; however, it is often unsuccessful and rarely recovers a significant portion of the gastric contents. Gastric lavage is a procedure which has been relied upon for over a century. Its effectiveness is dependent on the nature, form, and dosage of the poison, latency between time of ingestion and lavage, and technique. In clinical experiments studying gastric lavage, it has been noted that the procedure is most beneficial 1 to 2 hours postingestion for the majority of poison ingestions. Lavage also provides an excellent route for activated charcoal and selected antidotes. Gastric lavage may pose several risks to the patient, including obstruction and contamination of the airways and oesophageal damage. Contraindications for gastric lavage are similar to those for emesis except that it may be safer to use in obtunded, comatose, or uncooperative patients. Cathartics used during initial poisoning therapy are usually the saline cathartics. They elicit an osmotic reaction in the small intestine which results in increased intraluminal fluid bulk, hyperperistalsis, and subsequent propulsion of contents. Cathartics have also been shown to stimulate the secretion of cholecystokinin, which is thought to have similar effects on the intestine. Cathartics have not been shown to significantly enhance drug elimination from the gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gastric emptying. Risk versus benefit in the treatment of acute poisoning. 378 40

Dopamine and apomorphine were injected directly into limbic, extrapyramidal and cortical areas of mouse brain to determine relative sensitivities to the inhibitory effects of these agents on mouse spontaneous climbing behaviour. Injections of 0.06-2 micrograms apomorphine or dopamine into the nucleus accumbens, central area of the amygdala, septum or ventral tegmental nucleus caused dose-dependent motor inhibition with maximal reductions in the order of 60-70% of control value. In the extrapyramidal nuclei, caudate-putamen and globus pallidus, apomorphine and dopamine were required at 0.5-2.5 micrograms to produce inhibition, but the degree of inhibition never achieved 50% of control. Apomorphine and dopamine (0.001-10 micrograms) failed to cause any inhibition of mouse spontaneous climbing behaviour when injected into the anteromedial, supragenual or suprarhinal cortex. The higher doses of dopamine or apomorphine could effect stimulation of climbing behaviour from the limbic, extrapyramidal and cortical areas. Bilateral injections of haloperidol or (-)sulpiride (0.001-1 microgram) into the selected limbic and extrapyramidal areas caused dose-related depression of mouse spontaneous climbing, the limbic areas, particularly the nucleus accumbens, being the most sensitive. Doses of these neuroleptics selected as having minimal effect in their own right were shown to antagonise the marked motor inhibition effected by dopamine and apomorphine from the limbic areas, and the modest inhibition effected from the extrapyramidal areas. In contrast, intracerebral pretreatments with prazosin or yohimbine failed to antagonise the motor inhibitory effects of dopamine or apomorphine from any brain area.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dopamine agonist action in mesolimbic, cortical and extrapyramidal areas to modify spontaneous climbing behaviour of the mouse. 392 17


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