Biochemical challenges for testing novel anti-panic drugs in humans.

Current medications for panic disorder each carry significant limitations that indicate the need for novel anxiolytics. The high costs and low success rates of drug development demand that testing trials be efficient. Lab panicogenic challenges in humans allow for the rapid biochemical induction of panic symptoms and hence an efficient means of testing potential anti-panic drugs.

Building neural networks within the academy: connecting neuroscience to other disciplines.

Never before in human history has there been a more exciting time to be studying neuroscience. By extension, the opportunities have never been greater to examine how contemporary findings in neuroscience might relate to other areas of human inquiry. Over the last two decades I have participated in a number of formal and informal attempts to connect neuroscience and psychology to other academic disciplines in the context of interdisciplinary courses.

Effects of beta-CCE on retention of aversively- and appetitively-motivated tasks in rats.

Beta-carboline-3-carboxylic acid ethyl ester (beta-CCE; 1.0 or 5.0 mg/kg, i.

Possible involvement of an endogenous benzodiazepine receptor ligand of the inverse agonist type in the regulation of rapid-eye movement (REM) sleep: an hypothesis.

1. Rapid-eye movement (REM) sleep is a complex behavioral state characterized by desynchronized electroencephalographic (EEG) activity, postural atonia, rapid, saccadic movements of the eyes, and vivid dreaming. 2.

Prevention and reversal of dopamine receptor supersensitivity by cyclo(leucyl-glycyl) (CLG): biphasic dose-response curves.

Chronic administration (21 days) of haloperidol (HAL) (IP, 1.0 mg/kg/day) induced a behavioral supersensitivity (stereotypic sniffing) to dopamine (DA) agonists (apomorphine) and upregulation (increased Bmax for sulpiride-inhibitable [3H]spiroperidol binding) of striatal and limbic D2 DA receptors (DAr). Coadministration of cyclo(leucyl-glycyl) (CLG; 8mg/kg, SC; every third day, every other day, but not every day) with HAL attenuated the behavioral supersensitivity.

Long-lasting dopamine receptor up-regulation in amphetamine-treated rats following amphetamine neurotoxicity.

Amphetamine (A) (9.2 mg/kg, IP), in combination with iprindole (I) (10.0 mg/kg, IP), caused long-lasting dopamine (DA) depletions in striatum (-49%, 4 weeks) but not in nucleus accumbens following one A/I injection.

Neurochemical basis for the absence of overt "stereotyped" behaviors in rats with up-regulated striatal D2 dopamine receptors.

Because of substantial evidence for the hyperdopaminergic hypothesis of tardive dyskinesia (TD), animal models, especially rats, treated chronically with neuroleptics continue to be used to study this disorder. The rat model has been criticized because, unlike TD, in rats there is an apparent lack of spontaneous abnormal movements even when striatal D2 dopamine receptor (DAr) density is substantially increased. Our data suggest a mechanism by which rats suppress these abnormal movements normally associated with elevated DAr levels.

The effects of cyclo(leucyl-glycyl) on nigrostriatal dopaminergic supersensitivity--inhibition of apomorphine-induced climbing.

In a previous study we showed that cyclo(leu-gly) (CLG) prevents the behavioural supersensitivity induced in the mesolimbic dopamine (DA) tract (in mice) by chronic haloperidol (HAL). In the current study, we evaluated the effects of CLG on supersensitivity to DA agonists in the nigrostriatal DA tract induced by chronic HAL (1.0 mg/kg, i.

Effects of amnesic doses of reserpine or syrosingopine on mouse brain acetylcholine levels.

The effects of reserpine and syrosingopine on mouse whole brain acetylcholine levels were examined. At 2 or 24 hr following injection, the brains were removed and analyzed by mass spectrometry. No differences were found between drug-treated and control mice in the acetylcholine content of the brain at either time interval.

Clinical-pharmacokinetic investigations of acetylsalicylic acid in cases of imminent premature delivery.

The pharmacokinetics of acetylsalicylic acid have been examined in a dose of 3.6 g per day (0.9 g every 6 h) for 4 days, and the effect of the drug in 25 gravidae, threatened by premature delivery, has also been studied.

Correlation between serum concentration and hypoglycemic effect of chlorpropamide in man.

The relationship between the serum concentration and some of pharmacokinetic parameters of chlorpropamide and the hypoglycemic effect of this drug was studied. Studies were carried out in a group of 18 patients in whom the concentrations of drug and sugar in blood were determined simultaneously. Close correlation between the concentration and some pharmacokinetic parameters of chlorpropamide and the intensity of decrease of the blood glucose level as well as the time of its occurrence has been found.

Biopharmaceutical evaluation of ferrous salts in form of oral long-acting tablets.

We determined the relative bioavailability in men of two preparations containing ferrous salts in the form of long-action tablets in relation to analogous conventional preparations in the from of drops and tablets. The comparison of the bioavailability of preparations slowly and quickly releasing the active substance did not show any prolonged effect and greater absorption of drugs slowly releasing the active substance along the alimentary tract.

Correlation between the total cholesterol serum concentration data and carbamazepine steady-state blood levels in humans.

The purpose of this study was to investigate the pharmacokinetics of carbamazepine at steady state, after multiple doses in patients with elevated serum cholesterol levels. Twelve patients participated in the investigation; patients were divided into two groups according to their total serum cholesterol levels. Each patient received multiple doses of carbamazepine 600 mg po once per day.

The effect of reserpine, syrosingopine, and guanethidine on the retention of discriminated escape reversal: peripherally administered catecholamines cannot reverse the reserpine amnesia in this situation.

In a series of experiments, the effects of reserpine, syrosingopine, and guanethidine on retention of a discriminated escape reversal training were investigated in mice. The peripherally and centrally acting reserpine produced amnesia while the primarily peripherally acting compounds, syrosingopine or guanethidine, did not produce amnesia even when given in high dosages or when training was given with low footshock. Unlike in the passive avoidance situation, peripherally administered norepinephrine or dopamine was not able to attenuate the reserpine-induced amnesia.