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Gen Pharmacol. 1992 Mar;23(2):177-85.
Comparative pharmacological profile of muscarinic agonists in the isolated ileum, the pithed rat, and the mouse charcoal meal transit test.

Williams PD, Colbert WE, Shetler TJ, Turk JA.

Lilly Research Laboratories, A Division of Eli Lilly and Company, Greenfield, IN 46140.

1. Several reportedly selective (McN-A-343, M1; RS-86, M2; pilocarpine, M3) and non-selective (oxotremorine, acetylcholine, cis-dioxalone, arecoline, muscarine) muscarinic agonists were examined for comparative pharmacological potency in three diverse models: the guinea pig ileum, the pithed rat, and the mouse charcoal meal transit test. 2. In the guinea pig ileum, all of the compounds examined were associated with concentration-dependent contractions. 3. The apparent order of potency in the isolated ileum was cis-dioxalone greater than acetylcholine greater than oxotremorine greater than arecoline greater than RS-86 greater than pilocarpine greater than McN-A-343. 4. The pA2 values for atropine and pirenzepine in the ileum ranged from 8.4 to 9.4 and 6.1 to 7.7, respectively, indicative of a single receptor, most likely M3. 5. In the mouse charcoal meal transit test, non-selective muscarinic agonists produced dose-dependent increases in gastrointestinal transit, while selective agonists failed to produce any significant changes. 6. Scopolamine methylbromide, a peripherally acting non-selective muscarinic antagonist, significantly reduced the ability of muscarine to increase transit. 7. The compounds were further examined for dose-dependent pressor effects in the pithed rat, which are known to be mediated by stimulation of M1-receptors in sympathetic ganglia. 8. McN-A-343 produced the greatest pressor response, as measured by the percent increase in mean pressure, followed by pilocarpine. 9. Pirenzepine antagonized the pressor response of McN-A-343 and pilocarpine in a dose-dependent manner.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1639230&dopt=Abstract




Neuroscience. 1990;38(3):609-19.
Coherence of compound field potentials reveals discontinuities in the CA1-subiculum of the hippocampus in freely-moving rats.

Bullock TH, Buzsaki G, McClune MC.

Neurobiology Unit, School of Medicine, University of California, San Diego, La Jolla 92093.

The ongoing micro-electroencephalogram was recorded with a chronically implanted comb-like array of 16 tungsten semi-microelectrodes 0.2 or 0.25 mm apart, spanning CA1 strata oriens, pyramidale and radiatum and into subiculum, in four behavioral states: walking, standing still, paradoxical and slow wave sleep and under scopolamine. Power, phase and coherence spectra were computed, the latter two for each of the 120 pairs, in frequency bands from 1 to 64 Hz. (1) Coherence is high for all frequencies within the same subfield, e.g. stratum radiatum, but falls with distance. Theta frequency (8 Hz), when prominent and widespread (during "theta states" walking and paradoxical sleep), shows the most widespread synchrony: coherence falls slowly, from 1.0 at 0.2 mm to 0.7 at c. 2 mm longitudinally within stratum radiatum; all other frequencies fall two or three times faster. (2) An abrupt drop in coherence occurs across field borders (CA1-subiculum) and between stratum oriens and radiatum, across a line just under stratum pyramidale, between high coherence regions on each side of the coherence discontinuity. A less extreme drop occurs in stratum radiatum 0.4 mm from the subiculum border, without obvious histological correlate. The discontinuities in coherence are stable through all four behavioral states as well as under scopolamine. (3) Phase profiles diagonally across CA1 and into subiculum show abrupt, local shifts of phase (up to 125) at these same levels. No gradual shift reaching 180 (phase reversal) occurs in the span of loci examined. (4) The theta power peak in theta states is not necessarily due to additional energy in that band; in some conditions it is mainly due to reduced power in other frequencies. Root mean square voltage is generally less in the high theta ("synchronized") than in the non-theta states. Only the theta peak correlates with a peak in coherence. (5) Significant microstructure in the dynamics of neuronal cooperativity distinguishes behavioral states and regions of the hippocampal cortex.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2270136&dopt=Abstract




Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993 Nov;13(11):675-6, 646.
[Effect of improving memory and inhibiting acetylcholinesterase activity by invigorating-qi and warming-yang recipe]

[Article in Chinese]

Liu ZY, Yang YG, Zheng B.

Hunan Institute of TCM, Changsha.

Invigorating-Qi and Warming-Yang (IQWY) had a good curative effect to some senile diseases such as senile dementia, senile hypomnesia etc. This experiment was designed for probing into the therapeutical mechanism of IQWY recipe. BALB/C pure bred mice were divided into five groups. Group I was taken per os of invigorating Qi (IQ), Group II warming Yang (WY), Group III IQWY drugs, Group IV was dysmnesia model, and Group V blank control group injected with normal saline only. All groups except Group V were injected scopolamine (5mg/kg) intraperitoneally to induce dysmnesia model after medication. IQ drug consisted of Codonopsis pilosula, Astragalus membranaceus, Poria cocos, and Glycyrrhiza uralensis, WY drug of Cynomorium songoricum, Epimedium brevicornum and Cuscuta chinensis, while IQWY recipe consisted of both IQ and WY drugs. The results showed that IQ, WY and IQWY had an evident antagonistic action to Scopolamine induced dysmnesia mice, and could improve their memory. The erroneous times of the animal's reaction in Group I, II and III were less than those in Group IV, P < 0.05 or P < 0.01. Acetylcholinesterase (AchE) activity in the mice could be inhibited by IQ, WY and IQWY also. The activity in Group I, II and III was less than that in Group IV and V, P < 0.05 or P < 0.01. The therapeutic mechanism of IQWY was in connection with its effect to M-cholinergic transmitters of central nervous system.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8155947&dopt=Abstract













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