Topiramate Inhibits Trigeminovascular Neurons in the Cat

Cephalalgia ◽  
2004 ◽  
Vol 24 (12) ◽  
pp. 1049-1056 ◽  
Author(s):  
RJ Storer ◽  
PJ Goadsby
Keyword(s):  
Cumulative Dose ◽  
Dose Response ◽  
Sensory Input ◽  
Superior Sagittal Sinus ◽  
Maximum Effect ◽  
Response Curves ◽  
Sagittal Sinus ◽  
Dose Dependent Fashion ◽  
Dose Response Curves ◽  
Dose Dependent

To facilitate understanding the action of antimigraine preventives the effect of topiramate on trigeminocervical activation in the cat was examined. Animals ( n = 7) were anaesthetized and physiologically monitored. The superior sagittal sinus (SSS) was stimulated to produce a model of trigeminovascular nociceptive activation. Cumulative dose-response curves were constructed for the effect of topiramate at doses of 3, 5, 10, 30 and 50 mg/kg on SSS-evoked firing of trigeminocervical neurons. Topiramate reduced SSS evoked firing in a dose-dependent fashion. The maximum effect was seen over 30 min for the cohort taken together. At 3 mg/kg firing was reduced by 36 ± 13% (mean ± SEM) after 15 min. At 5 and 50 mg/kg firing was reduced by 59 ± 6% and 65 ± 14%, respectively, after 30 min. Inhibition of the trigeminocervical complex directly, or neurons that modulate sensory input, are plausible mechanisms for the action of preventives in migraine.

Prostaglandin fevers in rats: regulated change in body temperature or change in regulated body temperature?

1989 ◽  
Vol 257 (4) ◽  
pp. R695-R699 ◽  
Author(s):  
J. D. Feng ◽  
M. Price ◽  
J. Cohen ◽  
E. Satinoff
Keyword(s):  
Body Temperature ◽  
Dose Response ◽  
Dark Cycle ◽  
Response Curves ◽  
Vehicle Injection ◽  
Dose Dependent Fashion ◽  
Dose Response Curves ◽  
Dose Dependent ◽  
Light Part

Experiments examining the effects of central injections of E-series prostaglandins (PGE) on body temperature have only been done in the light part of a light-dark cycle. The present experiments examined the characteristics of fevers in rats after intraventricular PGE2 injections in both light and dark in a 12:12 h photoperiod. In the light, the change in body temperature (Tb) after 0.5 microgram was not significantly different from the change after vehicle injection. After injection of PGE2 (1, 2, 4, and 8 micrograms), Tb rose in a dose-dependent fashion. Mean initial Tb in the light was 36.4-36.6 degrees C. Tb rose a mean of 1.5 degrees C after 1 microgram, 1.9 degrees C after 2 micrograms, 2.7 degrees C after 4 micrograms, and 3.5 degrees C after 8 micrograms PGE2. A dose of 16 micrograms gave almost identical results as 8 micrograms. In the dark, mean initial Tb was 37.4-37.7 degrees C. Tb rose less than 0.8, 1.1, 1.4, and 2.3 degrees C after 1-8 micrograms PGE2, respectively. Thus there were two distinct dose-response curves for day and night. Nevertheless, peak Tb values attained in the two conditions were not significantly different from each other at any given dose. These results show that a particular dose of PGE2 raises Tb to a particular level, largely independent of either the Tb at the time of the injection or the phase of the light-dark cycle. However, the change in Tb at any dose depends strongly on initial Tb. Therefore, we urge researchers in the pharmacology of thermoregulation to report initial and final Tb values as well as changes in Tb.

Pentobarbital and contraction of vascular smooth muscle

1975 ◽  
Vol 229 (6) ◽  
pp. 1635-1640 ◽  
Author(s):  
BT Altura ◽  
BM Altura
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Dose Response ◽  
Mechanical Activity ◽  
Response Curves ◽  
Aortic Smooth Muscle ◽  
Dose Response Curves ◽  
Portal Veins ◽  
The Right ◽  
Dose Dependent

This study, with isolated rat aortic strips and portal veins, was undertaken to : 1) study the effects, if any, of pentobarbital Na (PTB) (5 x 10(-5) to 2 X 10(-3) M) on reactivity to epinephrine, serotonin, and KCl; 2) determine whether certain concentrations of PTB induce direct actions on aortic strips and portal veins; and 3) gain some insight into how these effects are brought about. The results indicate that PTB can: a) inhibit development of spontaneous mechanical activity in these vessels in anesthetic concentrations; b) dose-dependently attenuate contractions induced by epinephrine, serotonin, and KC1; c) cause a noncompetitive type displacement of the dose response curves of these vasoactive agents; d) attenuate Ca2+- induced contractions of potassium-depolarized aortic strips and portal veins concomitant with a dose-dependent displacement of these dose-response curves to the right; and e) rapidly relax drug as well as Ca2+ -induced contractions of aortas and portal veins. In addition, the data indicate that rat portal venous smooth muscle is more sensitive to the inhibitory actions of PTB than rat aortic smooth muscle. Overall, these data suggest that concentrations of PTB used to induce surgical anesthesia can exert profound depressant effects on at least two different types of vascular smooth muscle that may be related to actions on movement and/or translocation of Ca2+.

Methacholine dose-response curves in normal and asthmatic man: Effect of starting conductance and pharmacological antagonism

1984 ◽  
Vol 66 (6) ◽  
pp. 665-673 ◽  
Author(s):  
K. F. Chung ◽  
P. D. Snashall
Keyword(s):  
Dose Response ◽  
Normal Subjects ◽  
Small Degree ◽  
Response Curves ◽  
Significant Difference ◽  
Positive Linear Correlation ◽  
Dose Response Curves ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Different Doses

1. The bronchial response of 11 normal and ten stable asthmatic subjects to increasing concentrations of methacholine aerosol was assessed by serial measurements of specific airways conductance (scaw) in a body plethysmograph. 2. Cumulative log dose-response curves were constructed. The threshold provocative dose of methacholine needed to cause a 35% fall in starting sCaw (pD35) and the steepest slope of the response were measured from each curve. 3. On separate days subjects were premedicated with 0.9% NaCl solution (control) in duplicate, chlorpheniramine, salbutamol and atropine, the last-named at two different doses, one twice the other. 4. Asthmatic subjects had a lower mean PD35 and a lower mean slope than normal subjects. 5. Pretreatment with salbutamol resulted in a greater increase in sGaw than after atropine but caused a smaller increase in PD35 in both groups. There was a dose-dependent increase in PD3s after the two doses of atropine, but no significant difference in bronchodilatation between doses. Mean steepest slope approximately doubled in these three sets of challenges. 6. Chlorpheniramine caused a small degree of bronchodilatation and there was a non-significant increase in mean PD3s and in mean steepest slope in both normal and asthmatic groups. 7. There was a positive linear correlation between starting sGaw and steepest slope in each group of premedicated challenges, such that when

scholarly journals Myorelaxant Effect of Essential Oil of Rhizome of Alpinia calcarata Rosc. on Rat Duodenal Smooth Muscle

2007 ◽  
Vol 2 (7) ◽  
pp. 1934578X0700200 ◽  
Author(s):  
Siddharth Pandey ◽  
Om Prakash ◽  
Anjum Zafar ◽  
Subrata K. Hore ◽  
Anil K. Pant ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Essential Oil ◽  
Dose Response ◽  
Response Curves ◽  
Competitive Antagonist ◽  
Rat Duodenum ◽  
Dose Response Curves ◽  
The Right ◽  
Dose Dependent

Analysis of the essential oil from the rhizome of Alpinia calcarata Rosc. (ACREO) by a combination of GC and GC-MS revealed the presence of 1,8-cineole (42.2%), endo-fenchyl acetate (14.7%), camphene (7.6%), β-pinene (6.9%), α-terpineol (5.3%) and camphor (5.0%). Twenty-three compounds were identified in the oil. ACREO showed dose dependent myorelaxant activity in rat duodenum. The dose response curves of acetylcholine (ACh) and CaCl2 were shifted by ACREO to the right with increases in EC50 values and decreases in Vmax. These findings suggest that ACREO is a non-competitive antagonist of ACh and calcium.

Increased contractility in vascular smooth muscle of dystrophic hamsters

1983 ◽  
Vol 61 (2) ◽  
pp. 182-185 ◽  
Author(s):  
E. G. Hunter ◽  
J. Elbrink
Keyword(s):  
Animal Model ◽  
Smooth Muscle ◽  
Muscular Dystrophy ◽  
Vascular Smooth Muscle ◽  
Cumulative Dose ◽  
Dose Response ◽  
Response Curves ◽  
Collagen Protein ◽  
Dose Response Curves

To investigate the "vascular" hypothesis of muscular dystrophy, the sensitivity and contractility of aortic spiral strips of dystrophic (BIO 14.6) and normal (FIB) hamsters have been determined to various smooth muscle agonists. The results obtained with cumulative dose–response curves show that there is no increase in the sensitivity of the dystrophic compared with the normal aorta to noradrenaline, phenylephrine, isoproterenol, histamine, or 5-hydroxytryptamine. However, there was a significant increase in the force generated by aortic strips of the dystrophic animals to all agonists. Determination of noncollagen and collagen protein showed that there was no difference in the relative proportions of these proteins in the aortas from the two strains. The results show that in this animal model of dystrophy an increased response to vasopressor amines occurs and is in accordance with that expected of the vascular hypothesis.

Sign in / Sign up

Export Citation Format

Share Document