Amitriptyline-induced supersensitivity of a central muscarinic mechanism: Lithium blocks Amitriptyline- induced supersensitivity

Chronic treatment with amitriptyline produces dose-dependent supersensitivity of a central muscarinic cholinergic mechanism involved in the regulation of core body temperature. The authors demonstrated that chronic treatment with lithium prevents the induction of this response. The potential clinical and theoretical significance of this finding is set forth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27190/1/0000193.pd

Chronic treatment with lithium produces supersensitivity to nicotine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28017/1/0000453.pd

Systematic approach to the development of plasma amino acid analysis by high-performance liquid chromatography with ultraviolet detection with precolumn derivatization using phenyl isothiocyanate

A reversed-phase liquid chromatographic method for the separation of 26 phenylthiocarbamyl derivatives of amino acids in human plasma in ca. 35 min. is described. The method used a C18 column (150 x 4.6 mm I.D., 3 [mu]m) thermostatted at 41[deg]C, and a simple multistep linear gradient of two solvents. Solvent A was 0.05 M sodium acetate (pH 5.1)--acetonitrile (98:2, v/v), and solvent B was water--acetonitrile (40:60, v/v). A simple and successful approach to the optimization of the conditions for the separation of the 26 amino acid derivatives was realized. In the initial phase of development, the composition of the gradient, its timings, the column temperature, the flow-rate and the mobile phase compositions were optimized. At the end the influence of pH was studied, and this approach led to a clear resolution of the 26 amino acids. The method was validated by accuracy, precision, and recovery studies, by analyzing patient samples, and by comparing the quality control sample results with the classical ion-exchange method.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30446/1/0000070.pd

Desipramine subsensitizes nicotinic mechanism involved in regulating core temperature

Desipramine HC1, 10 mg/kg i.p. twice daily, produced subsensitivity to the hypothermic effects of nicotine, 1 mg/kg, after 1 and 2 weeks of treatment in male Sprague-Dawley rats. Phenelzine sulfate, fluoxetine HC1, and bright artificial light produced the same effect. The capacity of three chemically distinct classes of antidepressants and bright artificial light (a treatment for seasonal depression) to produce this result suggests that effects on nicotinic mechanisms may be involved in the mechanism of action of these treatments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27236/1/0000243.pd

Phenelzine produces subsensitivity to nicotine

Dilsaver, Steven C., Meenatshisundanan Hariharan, Robin K. Davidson: Phenelzine Produces Subsensitivity to Nicotine. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1993, 17(5): 847-860. 1. 1. The authors attempted to detect a possible effect of treatment with phenelzine on a physiological response to nicotine in the rat.2. 2. Positive findings in an animal model suggest the feasibility of more complicated experiments in animals and the possibility of studies involving human subjects.3. 3. Treatment of Sprague Dawley rats (n = 10) with phenelzine sulfate (15.0 mg/kg ip) every 48 hours for 14 days was associated with a 73.3% decrease in the hypothermic response to nicotine.4. 4. Treatment with phenelzine did not enhance the rate of elimination of nicotine.5. 5. The authors discuss a possible relationship between changes in nicotinic mechanisms and the therapeutic actions of drugs used to treat affective illness.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30616/1/0000256.pd

Caffeine and human cerebral blood flow: A positron emission tomography study

Positron emission tomography (PET) was used to quantify the effect of caffeine on whole brain and regional cerebral blood flow (CBF) in humans. A mean dose of 250 mg of caffeine produced approximately a 30% decrease in whole brain CBF; regional differences in caffeine effect were not observed. Pre-caffeine CBF strongly influenced the magnitude of the caffeine-induced decrease. Caffeine decreased paCO2 and increased systolic blood pressure significantly; the change in paCO2 did not account for the change in CBF. Smaller increases in diastolic blood pressure, heart rate, plasma epinephrine and norephinephrine, and subjectively reported anxiety were also observed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28939/1/0000776.pd

Positive and negative symptoms in schizophrenia and the dexamethasone suppression test

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28016/1/0000452.pd

Alpha2-adrenoceptor status in obsessive-compulsive disorder

Ten patients with obsessive-compulsive disorder (OCD) and 13 normal control subjects received intravenous infusions of 2 x 10-6 g/kg of clonidine and normal saline on separate days. Responses to the drug relating to plasma growth hormone (GH), 3-methoxy-4-hydroxyphenylglycol (MHPG), heart rate, blood pressure, and several symptoms were determined. Additionally, platelet alpha2-adrenoceptor binding was measured in most of the subjects. GH, MHPG, blood pressure, and heart rate responses to clonidine did not differ between groups. As expected, patients reported more symptoms than normal subjects, and clonidine was sedating for both groups. Patients did not differ from normal subjects in the symptom response to clonidine. The maximum number of binding sites (Bmax) for tritiated clonidine was significantly greater in OCD patients than in normals. This pattern of alpha2-adrenoceptor status is different than the patterns in major depression and panic anxiety.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28569/1/0000372.pd

Noradrenergic response to intravenous yohimbine in patients with depression and comorbidity of depression and panic

Adrenergic response following infusions of yohimbine or normal saline was evaluated in 9 control subjects, 8 patients suffering from a major depressive episode (MDE), and 12 patients suffering from concurrent MDE and panic disorder (MDE+P). Blood was drawn at -20, 0, 5, 10, 20, 45, and 90 min following the infusions, and assayed for norepinephrine (NE) and 3-methoxy-4-hydroxy-phenyl glycol (MHPG). Although the patient groups exhibited higher baseline NF concentrations, and a greater NE area under the plasma concentration versus time curve (AUC0-90) during the yohimbine infusion, the differences were not statistically significant. Baseline NE was significantly correlated with the NE AUC0-90 in all three groups, suggesting that, although the NE system may be dysregulated in the MDE and MDE+P patients, the NE system still appears to respond somewhat predictably following a challenge, even though the actual magnitude of response may vary.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30516/1/0000146.pd

The effect of paroxetine on thiothixene pharmacokinetics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72596/1/j.1365-2710.1997.95175951.x.pd