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N W Pedigo

Publications and source records attributed to N W Pedigo.

27 records · Page 2Linked to original sources
PubMed1981

Discrimination of multiple [3H]5-hydroxytryptamine binding sites by the neuroleptic spiperone in rat brain.

Certain neuroleptic drugs, such as spiperone and (+) butaclamol, can discriminate between two populations of [3H]5-hydroxytryptamine ([3H]5-HT) binding sites in rat brain. The butyrophenone neuroleptic spiperone shows the greatest selectivity for these two binding sites, having at least a 3000-fold difference between its dissociation constants (2-12 nM versus 35,000 nM) for the high- and low-affinity sites, respectively. Inhibition of [3H]5-HT binding by spiperone in rat frontal cortex and corpus striatum yields distinctly biphasic inhibition curves with Hill slopes significantly less than unity. Results from nonlinear regression analysis of these inhibition studies were consistent with a two-site model in each brain region. In the frontal cortex the high-affinity neuroleptic sites comprised about 60% of the total [3H]5-HT binding sites whereas in the corpus striatum they accounted for only 20% of the sites. Furthermore, saturation studies of [3H]5-HT binding assayed in the absence or presence of 1 microM-spiperone (a concentration that completely blocks the high-affinity site while having minimal activity at the low-affinity site) reveal a parallel shift in the Scatchard plot with no change in the dissociation constant of [3H]5-HT, but a significant decrease (64% in frontal cortex or 28% in corpus striatum) in the number of specific binding sites. These observations are consistent with the existence of at least two populations of [3H]5-HT binding sites having a differential regional distribution in rat brain.

Animals↗
PubMed1981

Multiple 3H-5-hydroxytryptamine binding sites in rat brain.

1. The effects of spiperone on 3H-5-HT binding to membranes prepared from rat diencephalon and lower brain stem were studied for comparison with telencephalic structures. 2. The neuroleptic spiperone produced shallow, complex inhibition curves of 3H-5-HT binding in the non-telencephalic areas, suggesting the presence of different types of high-affinity 3H-5-HT binding sites. However, the shape of the curves from the non-telencephalic areas differed from those of telencephalic regions. For example, there was a tendency for low concentrations of spiperone to cause an increase in binding in the diencephalon and lower brain stem rather than a decrease as seen in telencephalic areas. 3. In a search for other compounds which, like spiperone, could discriminate between the different types of 3H-5-HT binding sites in rat telencephalon, it was found that most drugs show little difference in their affinities for the two sites. However, one compound, AHR 1709B, was found to be about 10 times more potent in rat frontal cortex than corpus striatum, indicating that it can differentially recognize the two binding sites. 4. These results are consistent with the existence of multiple types of 3H-5-HT binding sites in the rat brain, and they define regional differences that had not previously been described. In addition, a new compound which can discriminate between different types of 3H-5-HT binding sites has been found, leading the way to the study of a series of new drugs which may selectively alter serotoninergic function.

Animals↗
PubMed1980

Placental beta-endorphin-like peptides.

Acid extract of human placental tissue contain, by both radioimmunoassay and radioreceptor assay, beta-endrophin-like material. Half of this material will not go through a 5000-dalton filter and on Sephadex G-200 has a molecular size between 25,00 and 50,000 daltons. Of the material going through a 5000-dalton ultrafilter, 80 percent is excluded on Sephadex G-25 and held back, very slightly, on Bio-Rad P6, indicating a molecular size of approximately 4500 to 4800 daltons. Thus, placenta appears to have macromolecular precursors from which a beta-endorphin-like material is released, with a size approximately 12 amino acids longer than half of the pituitary hormone.

Endorphins↗
PubMed1979

Inhibition of in vivo 3H-spiperone binding by the proposed antipsychotic Des-Tyr1-gamma-endorphin.

The proposed antipsychotic neuropeptide des-tyrosine1-gamma-endorphin (DT gamma E, beta LPH62,77) inhibits in vivo 3H-spiperone binding in the hypothalamus, corpus striatum and mesolimbic areas of rat brain. The neuroleptic drug haloperidol produces similar effects in these areas as well as in frontal cortex, but is considerably more potent than DT gamma E. Correspondingly, haloperidol produces postural and motor abnormalities not seen with DY gamma E. These data together with the results from previous in vitro studies suggest DT gamma E might act indirectly, having a selective neuroleptic-like action at 3H-spiperone binding sites.

Animals↗
PubMed1975

Determination and characterization of the antinociceptive activity of intraventricularly administered acetylcholine in mice.

Antinociceptive activity of intraventricularly administered acetylcholine was quantitated in mice by the tail-flick and phenylquinone tests. Acetylcholine was administered intraventricularly under light ether anesthesia in a 5 mul volume of sterile saline and mice were retested 10 minutes after the operation. A dose-response curve was established for acetylcholine (ED50 equals 7.3 mug) which was potentiated by intraventricular neostigimine and blocked by intraperitoneal atropine, but not by atropine methyl nitrate or mecamylamine. The antinociceptive effect of morphine was potentiated by intraventricularly administered acetylcholine. The acetylcholine-induced antinocieption was blocked by five narcotic antagonists in the same rank order of potency in which they antagonized the effects of morphine. However, the stereo-specificity of two narcotic antagonists, pentazocine and cylcazocine, was reversed in blocking acetylcholine and morphine-induced antinociception. The results of this study have established a phenomenon of acetylcholine-induced antinociception and identified the central, muscarinic nature of this response. In addition, several experiments have demonstrated similarities between this phenomenon and morphine-induced antinociception. These data implicate the possible involvement of central cholinergic mechanisms in the antinociceptive action of morphine.

Acetylcholine↗
PubMedDate not supplied

Cardiovascular effects of rectal methohexital in children.

STUDY OBJECTIVE: To define the cardiovascular effects of rectal methohexital in children with normal cardiac function. DESIGN: Cardiovascular evaluation of each patient was performed before and after medication. Each patient's predrug results were used as control measurements for comparison with measurements made after methohexital administration. SETTING: Inpatient operating room induction area in a privately endowed philanthropic children's hospital. PATIENTS: Forty-seven children age 35 +/- 22 months (mean +/- SD) scheduled for elective orthopedic or plastic surgery, free of cardiac or pulmonary disease, and receiving no medication with central nervous system activity. INTERVENTIONS: Control measurements of heart rate (HR), blood pressure (BP), and echocardiographic evaluations were obtained on the day before scheduled surgery. Repeat measurements were performed after the onset of methohexital-induced sleep. The time span of the measurements was designed to include the period of peak plasma methohexital concentration. In the preoperative holding area, 30 mg/kg of a 10% methohexital solution was administered rectally. If sleep did not occur in 15 minutes, an additional 15 mg/kg was given. MEASUREMENTS AND MAIN RESULTS: HR increased markedly after rectal methohexital [126 +/- 23 beats per minute (bpm) to 144 +/- 21 bpm, p less than 0.001], and stroke volume (SV) decreased (24 +/- 9 ml to 21 +/- 8 ml, p less than 0.01). There were no significant changes in BP or cardiac index. The shortening fraction and ejection fraction remained within the normal range for this age-group. CONCLUSIONS: Rectal methohexital induces sleep in healthy pediatric patients with minimal cardiovascular side effects. The primary effects are increased HR and decreased SV.

Anesthesia, Rectal↗