Pindolol potentiates the effect of fluoxetine on hippocampal seizures in rats. Serotonin reuptake inhibitor, fluoxetine, dilates isolated skeletal muscle arterioles. Possible role of altered Ca2+ sensitivity. [From valium to the happy pill?] Rx drugs

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Neurosci Lett. 1999 May 21;267(1):61-4.
Pindolol potentiates the effect of fluoxetine on hippocampal seizures in rats.

Wada Y, Hirao N, Shiraishi J, Nakamura M, Koshino Y.

Department of Neuropsychiatry, Kanazawa University School of Medicine, Japan.

Recent studies have shown that behavioral and neurochemical changes induced by selective serotonin (5-HT) reuptake inhibitors such as fluoxetine are potentiated by coadministration of a 5-HT1A receptor antagonist. The present study assessed the effects of concomitant administration of fluoxetine and a 5-HT1A receptor antagonist, pindolol, on focal hippocampal (HIP) seizures elicited by electrical stimulation in rats. A 10 mg/kg dose of fluoxetine, which was ineffective by itself, produced a significant increase in the afterdischarge threshold of HIP seizures when combined with pindolol at 10 mg/kg. The inhibitory effect of this combination was eliminated by pretreatment with parachlorophenylalanine, a depletor of brain 5-HT. These findings suggest that treatments designed to increase 5-HT neurotransmission inhibit the generation of HIP seizures. A combination of fluoxetine with a 5-HT1A receptor antagonist could thus be therapeutically useful for the treatment of depressive symptoms in patients with epilepsy.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10400249&dopt=Abstract

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Br J Pharmacol. 1999 Jun;127(3):740-6.
Serotonin reuptake inhibitor, fluoxetine, dilates isolated skeletal muscle arterioles. Possible role of altered Ca2+ sensitivity.

Pacher P, Ungvari Z, Kecskemeti V, Koller A.

Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.

1. Inhibitors of serotonin reuptake in the central nervous system, such as fluoxetine, may also affect the function of vascular tissues. Thus, we investigated the effect of fluoxetine on the vasomotor responses of isolated, pressurized arterioles of rat gracilis muscle (98 +/- 4 microns in diameter at 80 mmHg perfusion pressure). 2. We have found that increasing concentrations of fluoxetine dilated arterioles up to 155 +/- 5 microns with an EC50 of 2.5 +/- 0.5 x 10(-6) M. 3. Removal of the endothelium, application of 4-aminopyridine (4-AP, an inhibitor of aminopyridine sensitive K+ channels), or use of glibenclamide (an inhibitor of ATP-sensitive K+ channels) did not affect the vasodilator response to fluoxetine. 4. In the presence of 10(-6), 2 x 10(-6) or 10(-5) M fluoxetine noradrenaline (NA, 10(-9)-10(-5) M) and 5-hydroxytryptamine (5-HT, 10(-9)-10(-5)M)-induced constrictions were significantly attenuated resulting in concentration-dependent parallel rightward shifts of their dose-response curves (pA2 = 6.1 +/- 0.1 and 6.9 +/- 0.1, respectively). 5. Increasing concentrations of Ca2+ (10(-4) 3 x 10(-2) M) elicited arteriolar constrictions (up to approximately 30%), which were markedly reduced by 2 x 10(-6)M fluoxetine, whereas 10(-5)M fluoxetine practically abolished these responses. 6. In conclusion, fluoxetine, elicits substantial dilations of isolated skeletal muscle arterioles, a response which is not mediated by 4-AP- and ATP-sensitive K+ channels or endothelium-derived dilator factors. The findings that fluoxetine had a greater inhibitory effect on Ca2+ elicited constrictions than on responses to NA and 5-HT suggest that fluoxetine may inhibit Ca2+ channel(s) or interfere with the signal transduction by Ca2+ in the vascular smooth muscle cells.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10401565&dopt=Abstract

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Tidsskr Nor Laegeforen. 1999 Jun 10;119(15):2157-60.
[From valium to the happy pill?]

[Article in Norwegian]

Thormodsen M, Hjortdahl P, Farbrot T, Jacobsen OV, Nenningsland JB, Nielsen BB, Nielsen BB.

Farsund apotek.

The National Health Insurance started to refund expenditure on selective serotonin reuptake inhibitors in 1994. Questions have been raised if a significant portion of benzodiazepine users would transfer to these new drugs when they were described in the literature as also being used for light anxiety, but not carrying the addiction risk associated with benzodiazepines. The study looks at changes over a four-year period in the prescription of benzodiazepines and selective serotonin reuptake inhibitors dispensed from two pharmacies in Vest-Agder County with a total customer base of 17,800. For four years we also followed the prescription of drugs in these two groups to 1,125 patients who had been prescribed benzodiazepines in 1994. Our data show that only 5% of those receiving benzodiazepines in 1994, whom we were able to track, changed to a selective serotonin reuptake inhibitor-only therapy. 18% used a combination of the two groups of drugs and 77% continued to use benzodiazepines as before. The increase in the number of patients receiving selective serotonin reuptake inhibitors during the study period is far greater than the increase measured by number of daily doses. Selective serotonin reuptake inhibitors seem to have little influence on the use of benzodiazepines in our pharmacies' area. Our findings indicate that instead of "from Valium to Prozac" the change during the years 1994-97 can be described as "from Valium to Valium and Prozac".

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10402907&dopt=Abstract

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