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991.
D. F. Story M. E. Story M. W. McCulloch W. Hope M. J. Rand 《Clinical and experimental pharmacology & physiology》1974,1(5):429-439
SUMMARY 1. Desipramine, nortriptyline, amitriptyline, imipramine and cocaine inhibit the uptake of 3 H-noradrenaline in isolated guinea-pig atria. The order of potency is as listed; the concentrations producing 50% inhibition are 0.026, 0.036, 0.193, 0.288 and 3.47 μM, respectively.
2. The effects of desipramine and amitriptyline in a range of concentrations (0.01–100 μM) were tested on the resting and stimulation-induced efflux of radioactivity from isolated guinea-pig atria in which adrenergic transmitter stores had been labelled with3 H-(-)-noradrenaline.
3. Stimulation-induced efflux is slightly enhanced by a low concentration (0.01 μM) of desipramine, but is markedly reduced by concentrations of 30 and 100 μM. With 100 μM, there is a marked increase in resting efflux.
4. Amitriptyline enhances stimulation-induced efflux to a greater extent than does desipramine, and the maximal effect is produced with a higher concentration (30 μM). With 100 μM, stimulation-induced efflux is not significantly altered from control and resting efflux is increased, but to a lesser extent than with 100 μM desipramine.
5. It is concluded that desipramine and amitriptyline exert more than one action on adrenergic transmission: in addition to inhibiting neuronal uptake of noradrenaline, they also release noradrenaline, and desipramine interferes with the release of transmitter in response to nerve stimulation. 相似文献
2. The effects of desipramine and amitriptyline in a range of concentrations (0.01–100 μM) were tested on the resting and stimulation-induced efflux of radioactivity from isolated guinea-pig atria in which adrenergic transmitter stores had been labelled with
3. Stimulation-induced efflux is slightly enhanced by a low concentration (0.01 μM) of desipramine, but is markedly reduced by concentrations of 30 and 100 μM. With 100 μM, there is a marked increase in resting efflux.
4. Amitriptyline enhances stimulation-induced efflux to a greater extent than does desipramine, and the maximal effect is produced with a higher concentration (30 μM). With 100 μM, stimulation-induced efflux is not significantly altered from control and resting efflux is increased, but to a lesser extent than with 100 μM desipramine.
5. It is concluded that desipramine and amitriptyline exert more than one action on adrenergic transmission: in addition to inhibiting neuronal uptake of noradrenaline, they also release noradrenaline, and desipramine interferes with the release of transmitter in response to nerve stimulation. 相似文献
992.
From clinical experience it is known that the hypotensive action of clonidine may be antagonized by simultaneously administrated desipramine. In the present experiments it has been demonstrated that pretreatment of anaesthetized cats with desipramine, imipramine, amitryptyline and protryptyline reduced the central hypotensive action of clonidine. Since both clonidine and the tricyclic antidepressive drugs were administered via the vertebral artery in low doses it may be concluded that the interaction occurs in the CNS, i.e. the rhombencephalon. The experiments suggest that interaction between tricyclic antidepressants and clonidine is not restricted to desmethylimipramine. Therefore combination of clonidine with these drugs should be avoided. 相似文献
993.
Stimulating electrodes were implanted into the dorsal central gray area (DCG) of rats. The animals were trained to bar press to decrement the aversive DCG stimulation current. Rats treated with 5-hydroxytryptophan (5-HTP), 75 mg/kg or 150 mg/kg, showed a dose-dependent reduction in decremental bar pressing. In a second study, animals received either chlorimipramine, 15 mg/kg, protriptyline, 15 mg/kg, or 5-HTP, 150 mg/kg. Chlorimipramine, a strong blocker of serotonin reuptake, and 5-HTP produced significant reductions in decremental bar pressing. Protriptyline, a weak serotonin reuptake blocker, produced no significant effect. These results suggest that serotonin reduces aversive neural mechanisms associated with the dorsal central gray area. 相似文献
994.
An assay procedure is presented using high-performance liquid chromatography and fluorescence detection for simultaneous determination of imipramine, desipramine, and their 2-hydroxylated metabolites in whole blood and various tissues of the rat. By modifying methods previously described for plasma, we have developed an assay method for sensitive, reproducible quantitation of these compounds in rat plasma, whole blood, brain, liver, and fetus. Increasing the volume of the extraction solvent (20% butanol in hexane) increased recovery of imipramine and desipramine to greater than 90% for all tissues examined. No interfering peaks were observed for any of the tissues studied. Addition of n-butylamine as a modifier to the mobile phase decreased the retention of all four compounds and decreased peak tailing of the demethylated compounds. The total elution time was less than 15 min. Using these methods the coefficient of variation for all four compounds was generally less than 5% for each of the five tissues examined. The calibration curves were linear for standard concentrations of 25–2,000 ng/ml spiked tissue homogenate. This method has sufficient sensitivity and specificity for use in pharmacokinetic studies of imipramine. 相似文献
995.
996.
Jean F. Menez Brian E. Leonard 《Progress in neuro-psychopharmacology & biological psychiatry》1986,10(6):703-708
1. The effects of the chronic administration of barbitone and its O2-substituted isopropyl derivative (02IB) was studied on the hypomotility induced in rats by the acute administration of a low dose of apomorphine.
2. Neither drug was found to selectively antagonize the hypomotility caused by acute apomorphine administration.
3. No correlation could be found between the behavioural effects of the barbiturates and changes in the concentrations of biogenic amines and GABA in four discrete brain regions.
4. The results of this study do not support the conclusions of previous acute studies in which O2IB has been shown to have an antidepressant profile. 相似文献
997.
The effects of new non-tricyclic amine uptake inhibitors, FS32 and FS97, on the uptake of [3H]-norepinephrine (NE) into the hypothalamic synaptosomes and [3H]-5-hydroxytryptamine (5-HT) into whole brain synaptosomes were studied. Their effects were compared with those of tricyclic antidepressants. The uptake of [3H]-NE was inhibited competitively by FS32 and FS97 with a respective Ki value of 6.5 × 10?7 M and 3.8 × 10?7 M. The potency of FS32 and FS97 to inhibit this uptake was almost comparable to that of clomipramine and imipramine, respectively. In the case of [3H]-5-HT uptake, FS32 and FS97 also showed competitive inhibition with a respective Ki value of 2.9 × 10?6 M and 5.9 × 10?6M. The ability of FS32 to inhibit [3H]-5-HT uptake was almost equal to that of nortriptyline, while FS97 was two times more potent than iprindole in inhibiting this uptake. 相似文献
998.
The effect of antidepressant drugs on regional cerebral glucose utilization in the rat 总被引:1,自引:0,他引:1
Joseph C. Gerber III Junichiro Choki David J. Brunswick Martin Reivich Alan Frazer 《Brain research》1983,269(2):319-325
The 2-deoxyglucose (2-DG) technique is a potentially powerful method for assessing the effect of centrally acting drugs on local neuronal function in the brain. Since little is established on the effect of antidepressant drugs on local functional activity throughout the brain, we have employed this technique to study the effects of desmethylimipramine (DMI), a tricyclic antidepressant, and assessing the effect of centrally acting drugs on local neuronal function in the brain. Since little is established on the effect of antidepressant drugs on local functional activity throughout the brain, we have employed this technique to study the effects of desmethylimipramine (DMI), a tricyclic antidepressant, and assessing the effect of centrally acting drugs on local neuronal function in the brain. Since little is established on the effect of antidepressant drugs on local functional activity throughout the brain, we have employed this technique to study the effects of desmethylimipramine (DMI), a tricyclic antidepressant, and phenelzine, a monoamine oxidase inhibitor used clinically as an antidepressant, on local glucose utilization. The drugs were administered either as an acute dose, or repeatedly for 7 days, or chronically for 28 days. The local metabolic rate of glucose was determined in 30 regions of rat brain. Acute DMI increased glucose utilization in 11 regions whereas, in contrast, chronic DMI decreased glucose utilization in 7 regions of rat brain. Many of the areas affected are those of the telencephalon and diencephalon that receive prominent noradrenergic innervation. This is consistent with the notion that acute DMI treatment leads to enhanced and chronic DMI treatment leads to reduced noradrenergic functioning in the CNS. In contrast to these effects with DMI, phenelzine had little effects on glucose utilization either after acute or chronic dosing. 相似文献
999.
S. Vandel G. Bertschy P. Baumann S. Bouquet B. Bonin T. Francois D. Sechter P. Bizouard 《Pharmacological research》1995,31(6)
The in vivo pharmacokinetic interaction between two selective serotonin reuptake inhibitors (SSRI) (fluvoxamine, fluoxetine) and tricyclic antidepressants (TCAs) (amitriptyline, clomipramine) or neuroleptics (haloperidol, cyamemazine, levomepromazine, propericiazine) was assessed in 29 in-patients. They were phenotyped twice with dextromethorphan and mephenytoin: first in steady state conditions while under treatment with TCAs or neuroleptics; and also 10 days after an associated treatment with fluvoxamine (150 mg day−1) or fluoxetine (20 mg day−1).A clear and statistically significant increase in the mean urinary metabolic ratio (MR) of dextromethorphan/dextrorphan and in the mean mephenytoin S/R ratio (S/R) was seen with the fluvoxamine and fluoxetine treatment. The mean MR increased from 0.13 to 0.27 (P<0.01) with fluoxetine and from 0.34 to 0.84 with fluvoxamine (P<0.05). The (dextromethorphan) “extensive metabolizer” phenotype switched to the “poor metabolizer” phenotype in six patients by the 10-day fluoxetine treatment, and in two patients by the fluvoxamine treatment. The mean S/R increased from 0.24 to 0.34 (P<0.05) with fluoxetine, and from 0.33 to 0.58 (P<0.002) with fluvoxamine.These results are in agreement with the observed modification of TCA plasma levels after the SSRI association. During fluvoxamine treatment, amitriptyline and clomipramine plasma levels (P<0.06 both) tendentially increased, and those of demethylclomipramine decreased (P<0.06). Fluoxetine addition lead to a significant increase (P<0.02) of the desmethylclomipramine plasma levels. Fluvoxamine induced a moderate augmentation of the plasma levels of haloperidol and its reduced metabolite and no change in the plasma levels of cyamemazine and levomepromazine. But patients treated with neuroleptics are to few to draw any firm conclusion.This study suggests, that fluoxetine and fluvoxamine differ in their interaction with the metabolism of some other basic psychotropic drugs, by a mechanism which implies CYP2D6 and CYPmeph and possibly other isoformes of cytochrome P-450. Moreover, the interactions produced varied with the TCA prescribed. 相似文献
1000.
Sodium lactate precipitates panic in 70-100% of clinically ill patients with panic disorders. The lactate vulnerability of remitted patients is unknown. In this study, 13 panic patients completed three sequential sodium lactate infusions: one before treatment, a second when panic free on tricyclic antidepressants (TCA), and a third when in remission and unmedicated for 1 to 6 months. Three out of 13 patients panicked at the third infusion as compared to 0/13 infused on TCA and 7/12 at pretreatment infusion. This result (1) indicates that lactate vulnerability can exist in clinically well, unmedicated patients, and (2) raises the possibility that lactate vulnerability may be a trait characteristic. Further studies are needed before definite conclusions can be drawn. 相似文献