Effect of prenatal diazepam, phenobarbital, haloperidol and fluoxetine exposure on foot shock induced aggression in rats. Impact of nonspecific binding to microsomes and phospholipid on the inhibition of cytochrome P4502D6: implications for relating in vitro inhibition data to in vivo drug interactions. Rx drugs

Drugs online research references

Indian J Exp Biol. 1998 Oct;36(10):1023-4.
Effect of prenatal diazepam, phenobarbital, haloperidol and fluoxetine exposure on foot shock induced aggression in rats.

Singh Y, Jaiswal AK, Singh M, Bhattacharya SK.

Department of Anatomy & Pharmacology, Banaras Hindu University, Varanasi, India.

Different groups of pregnant rats were treated with diazepam (10 mg/kg), phenobarbital (10 mg/kg), haloperidol (0.1 mg/kg), fluoxetine (10 mg/kg) and vehicle (normal saline) intraperitoneally once a day during gestation days 13 to 21. After birth these pups were culled to 8 pups/dam and foster-nursed by lactating mothers for 3 weeks and were reared in colony cages thereafter. Sex and weight matched pairs of rat offsprings were subjected to foot shock induced aggression test at 8 weeks of age. Two parameters of aggressive behaviour were recorded namely, the latency to fight and total number of fighting bouts. The results indicate that prenatal exposure to diazepam, phenobarbital, haloperidol and fluoxetine caused significantly enhanced aggression in terms of number of fighting bouts.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10356962&dopt=Abstract

note: kwd match prozac online literature

Drug Metab Dispos. 2003 May;31(5):606-11.
Impact of nonspecific binding to microsomes and phospholipid on the inhibition of cytochrome P4502D6: implications for relating in vitro inhibition data to in vivo drug interactions.

Margolis JM, Obach RS.

Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer Global Research and Development, Groton Laboratories, Groton, Connecticut 06340, USA.

The effects of microsomal concentration on the inhibitory potencies of four compounds--fluoxetine, quinidine, imipramine, and ezlopitant--on heterologously expressed recombinant CYP2D6-catalyzed bufuralol 1'-hydroxylase activity were determined. Increasing microsomal concentration from 0.0088 to 2.0 mg/ml, using additional microsomes not containing cytochrome P450, resulted in a marked increase in IC(50) and K(I) values for fluoxetine, ezlopitant, and imipramine, when inhibition constants were calculated using the nominal concentration of inhibitor added to the incubation mixture. The extent of nonspecific binding of these inhibitors to microsomes was determined using equilibrium dialysis. The extent of binding increased with increasing microsomal concentration. Binding was greatest for ezlopitant, followed by fluoxetine, imipramine, and quinidine. Correcting inhibition constants for the extent of nonspecific binding resulted in greater consistency of these values with differing microsomal protein concentrations. This effect was also studied with added phospholipid. Inhibition constants increased with increasing phospholipid, and nonspecific binding was also observed for these four drugs to phospholipid. This suggests that the phospholipid component of microsomes possesses some or all of the responsibility for nonspecific binding, and its effect on inhibitors of drug-metabolizing enzymes. These findings suggest that inhibition constants for drugs as inhibitors of microsomal drug-metabolizing enzymes, such as cytochrome P450, should be corrected for the extent of nonspecific binding to components of the in vitro matrix. The implications of this on the prediction of drug-drug interactions from in vitro data are discussed.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12695349&dopt=Abstract

note: kwd match prozac online literature

rockvax.rockefeller.edu

Both repeated stress and corticosterone administration induce remodeling of apical dendrites of hippocampal CA3 pyramidal neurons. Circulating glucocorticoids are involved in the mechanism that produces atrophy, along with excitatory amino acids and serotonin (5-hydroxytryptamine, 5-HT). We used 5-HT-related antidepressants and a benzodiazepine in order to explore indirectly the role of serotonin and GABA(A)-benzodiazepine receptors in the stress-induced structural changes visualized by the Golgi impregnation of the rat hippocampus. The 5-HT reuptake enhancer (+/-)-tianeptine prevented the dendritic atrophy caused by repeated restraint stress in a non-stereoselective fashion and two 5-HT reuptake antagonists, fluoxetine and fluvoxamine, failed to block dendritic atrophy. Tianeptine also functions as a therapeutic tool since it reversed the already established hippocampal atrophy caused by treatment with corticosterone for 3 weeks. Finally, the benzodiazepine agonist adinazolam was effective in preventing the stress-induced dendritic atrophy. These findings suggest that the synaptic availability of 5-HT is involved in the mechanism leading to stress-induced dendritic remodeling and supports the idea that the hippocampal inhibitory GABAergic tone may play a regulatory role.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10357248&dopt=Abstract

note: kwd match prozac online literature

Herbs and Pharmaceuticals Online || Hair Million herbal formula for hair loss and hair growth || Antibiotics and prescription medications online literature ||