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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several C-10 substituted cannabidiol (CBD) derivatives and novel oxepin derivatives of delta 9-tetrahydrocannabinol (delta 9-THC) were synthesized and evaluated for biological activity in mice and dogs. Treatment of 10-bromocannabidiol diacetate (3) with various amines in Me2SO gave the corresponding 10-aminocannabidiol derivatives 4-6. Similarly, treatment of 3 with NaN3 gave the azido compound 7, which with LiA1H4 afforded the 10-aminocannabidiol 9. However, reduction of 7 with CrCl2 formed the amide 8, which on further reduction with LiA1H4 gave the N-ethyl analogue 10. Coupling of 9 with 11 in the presence of dicyclohexylcarbodiimide formed 12, which was then deprotected with HCl to give the analogue 13. The oxepin analogue 14a was synthesized from 3 by treatment with Na2CO3 in CH3OH/H2O at room temperature. The dimethylheptyl analogue 14b was similarly prepared. Incorporation of N-ethyl (10), N-methyl-N-propargyl (6), and morpholino (4) groups in CBD at position 10 resulted in analogues that were more potent than CBD in producing hypoactivity in mice. These analogues had relatively little effect on rectal temperature. Selected substitutions at C-10 also resulted in analogues that were partially effective in blocking delta 9-THC antinociceptive activity. This blockade was observed particularly in compound 10, which also showed unusually toxic properties. Incorporation of a seven-membered oxepin in the delta 9-THC structure eliminated cannabinoid activity although substitution of the pentyl side chain with a 1,2-dimethylheptyl in the oxepin 14b resulted in CNS depression in mice.
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PMID:Hashish: synthesis and central nervous system activity of some novel analogues of cannabidiol and oxepin derivatives of delta 9-tetrahydrocannabinol. 298 18

Alfentanil, a short-acting and powerful analgesic, when injected peripherally to rats (0.5 mg/kg) produced a catatonic state characterized by a rigid akinesia. The present study was designed to explore the neuroanatomical location of the opiate receptors mediating the alfentanil induced catatonia. The catatonic effect of alfentanil was measured using a bar test and depression of locomotor activity in rats tested in photocell cages during an active nocturnal phase of their cycle. Methylnaloxonium HCl (MN), a quaternary derivative of naloxone which does not readily cross the blood-brain barrier, injected into the lateral ventricle significantly reduced the catatonia at doses of 0.125-2.0 micrograms as measured in both the locomotor and bar test. MN perfusion of similar doses directly into the nucleus raphe pontis, but not in the caudate nucleus significantly antagonized the catatonia. These data complement results on alfentanil-induced muscular rigidity (Blasco et al., see companion paper) where EMG indices of rigidity in rats were reversed by microinjections of low doses of MN (0.125 and 0.5 microgram) in the nucleus raphe pontis, but not the caudate nucleus even at a high dose (4.0 micrograms). Together these results suggest that the region of the nucleus raphe pontis is an important neural substrate for opiate-induced muscular rigidity, and that the catatonic state produced by opiates depends on more diffuse opiate receptor activation of which one important component may be the nucleus raphe pontis.
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PMID:'Catatonia' produced by alfentanil is reversed by methylnaloxonium microinjections into the brain. 302 82

The in situ isolated rodent larynx preparation can be utilized for the detection of peripheral opiate receptor antagonists. Measurements of peripheral opioid-induced laryngospasm and central opioid-induced respiratory depression can be made in each preparation. Fentanyl citrate was used to stimulate both peripheral and central opiate receptors and [D-Ala2-Met5] enkephalinamide was used to stimulate only peripheral opiate receptors. Compounds that inhibit both laryngeal and respiratory effects of fentanyl, e.g., naloxone HCl, can be considered both central and peripheral opiate receptor antagonists. Compounds that inhibit only the peripheral laryngeal effects of fentanyl, e.g., naltrexone methylbromide, can be considered peripheral opiate receptor antagonists. The description of this preparation provides a simple and sensitive anesthetized animal model for the detection and characterization of compounds acting at peripheral and/or central opiate receptors.
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PMID:The in situ isolated larynx for evaluating peripheral opiate receptor antagonists. 303 83

Effects of morphine on the rectal temperature and respiratory rate, and [3H]naloxone binding to brain membranes from seven brain regions were compared among six strains of male mice, including DBA/2N, C57BL/6N, BALB/c, C3H/HeN, A/J and ICR. The administration of 10 and 20 mg/kg doses of morphine HCl to these strains of mice decreased rectal temperature and respiratory rate. However, there was a significant strain difference in these two measures of the effect of morphine. The DBA/2N strain was the most sensitive in both measures of morphine action. The magnitude of hypothermia was positively correlated with respiratory depression among six strains of mice after the administration of 10 and 20 mg/kg morphine HCl, suggesting common mechanisms. Strain difference in naloxone binding in the brain regions could not explain that of the morphine responses, because there was no correlation between the intensity of morphine-induced hypothermia or respiratory depression and the regional [3H]naloxone binding for the mouse strains.
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PMID:Strain difference in the effects of morphine on the rectal temperature and respiratory rate in male mice. 309 May 93

Nizatidine is a potent and selective antagonist of histamine. The histamine-induced relaxation of the KCl-treated rat uterus was inhibited dose-dependently by nizatidine. The inhibition was characterized by displacement of the dose-response to histamine to the right, in parallel, without depression of the maximum. The affinity of nizatidine for the histamine H2-receptor of the rat uterus was about 10 times that of cimetidine. The steady-state dose-response acid outputs stimulated by histamine from the Heidenhain pouch and the gastric fistula were also shifted dose-dependently by nizatidine, in parallel, to the right. The inhibition was consistent with a surmountable antagonism of histamine. At high (10(-4) to 10(-3) M) concentrations, nizatidine increased the motility of the guinea pig stomach and duodenum in vitro; this effect was abolished noncompetitively by atropine (10(-8) M) and pyrilamine (10(-4) M). Both nizatidine and cimetidine administered s.c. showed "cytoprotective" action by reducing the gastric lesions induced by 1) aminoguinidine and pylorus ligation and 2) HCl plus aspirin in the rat. On a weight and molar basis, nizatidine was 4 and 5.25 times as effective as cimetidine, respectively. This cytoprotective action of nizatidine was found when acidity and total acid load in the stomach were not affected by the histamine H2-receptor antagonist.
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PMID:Actions of nizatidine on the rat uterus, dog stomach and experimentally induced gastric lesions. 309 39

A single intoxicating dose of chlordiazepoxide HCl (p.o.) in the rat can induce quantifiable manifestations of physical dependence. Dependence was revealed by antagonist precipitation (Ro 15-1788, CGS-8216) as well as spontaneous emergence of neurobehavioral signs of withdrawal observed by multiple raters blind to treatments. Ro 15-1788 was 45% more effective than CGS-8216 in both reversing chlordiazepoxide intoxication and expressing withdrawal signs. The severity of Ro 15-1788-precipitated withdrawal varied with chlordiazepoxide dose, Ro 15-1788 dose and the agonist-antagonist dose interval. Maximal precipitated dependence was evoked 3 days after chlordiazepoxide HCl (450 mg/kg) by Ro 15-1788 (25 mg/kg i.p.). The precipitated syndrome consisted of tail erection, reduced motor activity, high step, curled claw, arched back, muscle hypertonus and piloerection. Ro 15-1788-precipitated dependence emerged between 28 and 52 hr, peaked at 76 hr and disappeared by 124 hr. Spontaneous withdrawal had emerged from 100 to 124 hr and then faded gradually. The neurobehavioral expression of central nervous system depression and its reversal were necessary but not sufficient conditions for the induction and expression of acute chlordiazepoxide dependence. These results suggest caution in reviving acute benzodiazepine-overdosed patients to avoid iatrogenic withdrawal analogous to naloxone for opiates.
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PMID:Pharmacologic characterization of acute chlordiazepoxide dependence in the rat. 309 61

Three chick growth assays were conducted to investigate the effects of monensin on lysine and arginine utilization in crossbred chicks (New Hampshire X Columbian). Chicks were fed either a low lysine corn-sesame meal diet containing graded increments of crystalline lysine.HCl (Assay 1) or an arginine-deficient casein-dextrose diet (Assay 2) supplemented with graded levels of L-arginine.HCl in the presence or absence of supplemental monensin (121 mg/kg). Based upon analysis by slope-ratio methodology (i.e., gain regressed on supplemental amino acid intake), the efficiency of L-lysine or L-arginine utilization was found to be the same in both monensin-fed and control chicks. In Assay 3, effects of monensin on the lysine-arginine antagonism were studied. Chicks were fed an arginine-deficient casein-dextrose diet supplemented with 1 or 2% L-lysine.acetate in the presence or absence of supplemental monensin. Growth performance was depressed by feeding both levels of supplemental L-lysine.acetate. Monensin had no effect on the magnitude of the growth depression caused by supplemental lysine. These results support the view that neither lysine nor arginine utilization is impaired by feeding monensin.
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PMID:In vivo utilization of lysine and arginine in young chicks fed monensin. 313 6

Effects of respiratory and metabolic acidosis (pH approximately 6.8) on myocardial function were studied in the newborn and adult rabbits. Mechanical function was studied in the isolated arterially perfused heart preparation. Acidosis was induced either by increase of the perfusate PCO2 or by decrease of the bicarbonate content. During respiratory acidosis, developed tension (DT) decreased to 43 +/- 3% of control (n = 18) in the adult and this depression was significantly greater than in the newborn (DT = 92 +/- 4%, n = 6). Depression of DT by respiratory acidosis was observed even at high extracellular Ca. During metabolic acidosis, mechanical function decreased gradually and DT at 30 min into acidosis in the adult was 78 +/- 3% of control (n = 6). This depression of DT in the adult was significantly greater than in the newborn (DT at 30 min = 96 +/- 1% of control, n = 6). Statistical analysis using paired t test showed that respiratory acidosis, but not metabolic acidosis, caused significant negative inotropism in the newborn. Myofibrils were isolated and the ATPase was measured at 10(-8) to 10(-4) M Ca and at pH of 7.1 (control), 6.5, and 6.0. Reducing pH depressed the ATPase activity similarly in the newborn and adult. Intracellular buffer capacity was determined by titrating muscle homogenate with HCI. Although the initial pH was not different, addition of HCl to the homogenate caused less decrease in pH in the newborn. These data indicate that contractile function in the newborn heart is more resistant to acidosis and this may be due partly to the greater intracellular buffer capacity.
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PMID:Effect of acidosis on contractile function in the newborn rabbit heart. 315 69

Meperidine HCl was administered intramuscularly by hand-syringe to a number of individuals representing several species of cetaceans (n = 95) and pinnipeds (n = 36). Dosage administered was 0.11 mg/kg, 0.23 mg/kg or 0.45 mg/kg, with the majority of animals receiving the middle dosage. Meperidine HCl provided moderate restraint in cetaceans without obvious deleterious effects. Restraint was achieved rapidly, with maximum effect occurring 20 min after intramuscular injection and lasting for 2 to 3 hr. Analgesia appeared to last as long as 4 hr and was sometimes accompanied by a restoration of appetite in animals suffering from physical discomfort. Higher doses produced increased sedation and analgesia without noticeably depressing respiration. Meperidine HCl provided moderate restraint for phocids and walrus (Odobenus rosmarus) without apparent detriment. California sea lions (Zalophus californianus) showed little restraint, but demonstrated profound respiratory depression.
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PMID:The use of meperidine hydrochloride for chemical restraint in certain cetaceans and pinnipeds. 319 67

Propranolol hydrochloride is a beta-adrenergic blocking drug used in a variety of clinical conditions. Overdoses can result in severe hypotensive states usually associated with bradycardia or asystole or with profound myocardial depression. We report on an 18-year-old man who ingested a massive dose of propranolol HCl in a suicide attempt. The patient was brought to the hospital in an unresponsive state within 30 minutes of ingestion. He was initially stabilized but subsequently died nine hours after the drug was ingested. Invasive monitoring during this period revealed the shock to be secondary to marked depression of his systemic vascular resistance. Cardiac rhythm and left ventricular output were maintained throughout the attempted resuscitation. This hemodynamic picture suggests that decreased systemic vascular resistance may be another mechanism of shock in significant propranolol HCl overdoses.
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PMID:A fatal case of propranolol poisoning. 322 44


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