Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Protriptyline”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1986

Biochemical and pharmacological effects of fluperlapine on noradrenaline and acetylcholine systems in some rodent, bovine and crustacean preparations.

Fluperlapine was compared with clozapine, chlorpromazine, haloperidol and imipramine regarding its effects on some cholinergic and noradrenergic animal systems. Fluperlapine and clozapine showed the most pronounced anticholinergic effects. Fluperlapine was equipotent with clozapine in displacing [3H]-QNB from muscarinic receptors of the calf cerebral cortex (IC50 about 15 nM). In the mydriasis test in the mouse and in the crayfish hindgut bioassay the differences between fluperlapine and clozapine were small. Like the other antischizophrenic drugs tested, fluperlapine displayed a marked affinity for alpha 1-adrenoceptors (calf cerebral cortex: IC50 about 10 nM) but a negligible affinity for alpha 2-adrenoceptors in the same tissue. Only clozapine showed a weak affinity for the latter receptor type. Fluperlapine was as effective as imipramine in antagonizing tetrabenazine-induced ptosis in the rat, the anti-ptotic effect remaining constant after up to ten daily drug administrations. Still, imipramine was stronger than fluperlapine as an inhibitor of the accumulation of [3H]-noradrenaline ([3H]-NA) in rat cerebral cortex slices. Fluperlapine's effects on the spontaneous and the electrically-induced release of [3H]-NA from rat cerebral cortex slices, with and without protriptyline, showed it to be an inhibitor of the reuptake of NA. The results indicate that the pharmacological profile of fluperlapine is similar to that of clozapine, with additional antidepressant properties.

Acetylcholine↗
PubMed1976

The effect of tricyclic antidepressant drugs on the heart.

The effects on the heart rate and ECG of anaesthetised guines-pigs of amitriptyline, doxepin, imipramine and nortiptyline infused at 1.0 mg/kg/min until death were observed. In addition an in vitro study on guinea-pig atria was performed on the chronotropic and inotropic effects of these drugs and of desmethylimipramine and protriptyline at a concentration of 10(-5) M. The effect of sodium bicarbonate (3 mEq/kg i.v.) and propranolol (0.01--0.2 mg/kg i.v.) on amitriptyline and doxepin induced ECG changes was also assessed. A difference in the cardiac effects of the in vivo and in vitro model was observed. Guinea-pigs infused with doxepin survived significantly longer than those infused with amitriptyline, imipramine or nortriptyline. No statistically significant difference was found between the tricyclic drugs with respect to onset of widening of the QRS complex, increased PR and QT intervals. In the spontaneously beating atrial preparation doxepin was the most potent cardio-depressant. Sodium bicarbonate had no effect on arrhythmias induced by tricyclics, while propranolol, apart from the bradycardia induced, was without beneficial effect on the ECG. The guinea-pig provides a good model for studying the arrhythmogenic actions of tricyclic antidepressants.

Animals↗
PubMed1981

The functional role of the noradrenergic neurons in the thermoregulatory circuits in mice.

Intracerebroventricular (i.c.v.) treatment of mice with 6-hydroxydopamine (6-OHDA; 20--50 micrograms per mouse), which depletes brain noradrenaline (NA) and DA, completely prevents or significantly diminishes the hypothermic effect of various classes of drugs: dopaminomimetics--apomorphine (0.5--10 mg/kg), piribedil (40--100 mg/kg), bromocriptine (3 to 10 mg/kg), CM 29-712 (2--10 mg/kg), d, l-amphetamine (1--2 mg/kg), and L-DOPA (10--100 mg/kg) in combination with Ro 4-4602 (5--40 mg/kg); cholinomimetics--oxotremorine (0.04--0.05 mg/kg), arecoline (5--10 mg/kg) and pilocarpine (2--3 mg/kg); neuroleptics--chlorpromazine, promazine, perphenazine, chlorprothixene, haloperidol, fluanisone (5--10 mg/kg); central alpha-adrenoblocker aceperone (20--40 mg/kg); inhibitor of tyrosine-hydroxylase alpha-methyltyrosine (200--300 mg/kg); inhibitor of dopamine-beta-hydroxylase--disulfiram (150--250 mg/kg) and FLA-63 (15--25 mg/kg). This antihypothermic effect was demonstrated up to 3 months after administration of 6-OHDA for DA-mimetics and neuroleptics and up to 3 weeks for cholinomimetics. The hypothermic effect of presumable GABA-mimetics Phenybut (100--150 mg/kg) and Lioresal (10--25 mg/kg) was enhanced by a prior 6-OHDA treatment. Pretreatment of mice with desipramine (25 to 30 mg/kg i.p.), protriptyline (20 mg/kg) or AW 15(1)1129 (15--20 mg/kg) 20--45 min before 6-OHDA administration protects the central NA-ergic neurons from a destructive effect of 6-OHDA and partially or completely counteracts the antihypothermic as well as prohypothermic (in the case of GABA-mimetics) effect of 6-OHDA. In rats desipramine counteracted antihypothermic effect of 6-OHDA in the case of piribedil, but not of apomorphine. Intracerebroventricular treatment of mice with a low (15 microgram) dose of 5, 6-dihydroxytryptamine (5, 6-DHT) enhanced the hypothermic effects of DA-mimetics; higher doses of 5, 6-DHT (26 and 30 micrograms) and 5, 7-DHT (40 and 46 micrograms) diminished the hypothermic effects; the antihypothermic effect of 6-OHDA was stronger than that of equimolar doses of 5, 6- or 5,7-DHT; desipramine pretreatment counteracted antihypothermic effects of 5, 6-DHT and 5, 7-DHT as well as depletion of brain NA they produce. The data presented reveal the key position for NA-ergic neurons in a temperature regulation and, particularly, in effects of various drugs on body temperature in mice. The tentative fragment of the neuronal thermoregulatory circuit is proposed in attempt to account for the presented an other known data concerning drug action (and interactions) on core temperature in mice.

Animals↗
PubMed1984

Acute electrophysiologic effects of bethanidine sulfate in patients with ventricular tachycardia or fibrillation.

Ten patients with a history of ventricular tachycardia or ventricular fibrillation underwent electrophysiologic study with programmed stimulation before and 90 minutes after oral administration of bethanidine sulfate, 20 mg/kg. Mean plasma bethanidine concentration was 2.62 +/- 2.2 (+/- SD) micrograms/ml at the start of repeat testing. This dose of bethanidine produced no effect on sinus node function, atrioventricular conduction, or atrial or ventricular refractoriness. Ventricular tachycardia or fibrillation, inducible in all patients during the control study, could still be initiated by ventricular stimulation in 9 of 10 patients after bethanidine. Bethanidine suppressed the ability to initiate an arrhythmia in one patient with ventricular fibrillation during control stimulation. Orthostatic hypotension was seen in all patients despite pretreatment with the tricyclic antidepressant, protriptyline, 15 mg every 8 hours. The results suggest that bethanidine has few electrophysiologic effects and is of limited efficacy during electrophysiologic testing in patients with life-threatening ventricular arrhythmias.

Aged↗
PubMed1984

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate in primary ventricular fibrillation or life-threatening ventricular tachycardia.

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate, a chemical analog of bretylium tosylate, were studied using programmed cardiac electrical stimulation in 14 survivors of out-of-hospital cardiac arrest unassociated with acute myocardial infarction. Before bethanidine sulfate was administered sustained ventricular tachyarrhythmias (VT) were inducible in 11 patients and reproducible nonsustained VT was induced in 3 patients. Bethanidine sulfate shortened sinus cycle length and absolute and relative ventricular refractory periods measured during sinus rhythm, but did not alter ventricular effective refractory period measured during ventricular pacing. Bethanidine sulfate prevented inducible VT in 8 patients (57%), increased the number of extrastimuli needed to induce VT in 2 patients, and was ineffective in 4 patients. In contrast, in only 1 of 26 trials with other conventional and investigational antiarrhythmic drugs in these patients was VT prevented. Orthostatic hypotension was a prominent side effect of bethanidine sulfate therapy, but could be reversed in most patients by concomitant administration of protriptyline. Five patients in whom bethanidine sulfate was effective in the laboratory have been treated chronically (400 to 600 mg 4 times daily), and all are alive at 3 to 40 months. In the remaining 9 patients, 8 were treated empirically because no drug was effective in the laboratory and 1 was treated with quinidine, which appeared to be protective during testing. Four of these 9 patients, including the patient treated with quinidine, died suddenly during follow-up. Thus, although bethanidine sulfate therapy is difficult to initiate because of orthostatic hypotensive side effects, it may be useful in treating patients at high risk of recurrent cardiac arrest.

Adult↗
PubMed1984

Therapy of ventricular tachycardia.

Therapeutic modalities for ventricular tachycardia include antiarrhythmic drugs, direct current cardioversion, electrical pacing and surgical intervention. Lidocaine, procainamide and bretylium are all capable of controlling recurrent ventricular tachycardia; bretylium has the advantage of also being antifibrillatory and of raising the threshold for ventricular fibrillation. Lidocaine and bretylium are available only in i.v. form. Procainamide is available in i.v. as well as oral form. Other oral antiarrhythmic agents include quinidine, disopyramide, beta-blockers such as propranolol and verapamil. The latter may be useful in ventricular arrhythmias induced by ischemia; of these, only beta-blockers appear to significantly raise the threshold for ventricular fibrillation. Control of ventricular ectopy does not always preclude ventricular tachycardia and ventricular fibrillation. In treating ventricular tachycardia, bretylium tosylate is generally given 5 to 10 mg/kg i.v. over 10 to 20 minutes. Given too rapidly, it may cause nausea and vomiting. Orthostatic hypotension, a common side effect, generally abates with continued use and may be ameliorated with tricyclic antidepressants such as protriptyline. Significant supine hypotension may be encountered in patients with acute myocardial infarction and may be managed with pressor agents or fluids, or both. The antiarrhythmic efficacy of bretylium was analyzed in 40 patients. Five etiologic groups were defined by cardiac catheterization: 19 patients had atherosclerotic heart disease, 6 had primary myocardial disease, 4 had mitral valve prolapse, 4 had rheumatic heart disease and 7 had miscellaneous or no heart disease. All patients had recurrent ventricular tachycardia (VT); 23 had ventricular fibrillation (VF) as well. Other antiarrhythmic agents had failed in 38 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1980

Spinal noradrenergic terminal system mediates antinociception.

Intrathecal administration of norepinephrine (NE) into the lumbar subarachnoid space of rats and cats implanted with chronic spinal catheters produced a strong, dose-dependent, behaviorally defined analgesia. The effect appeared mediated by an alpha-receptor inasmuch as phenylephrine, but not isoproterenol produced the intrathecal effect. Moreover, the antinociceptive effect of NE was antagonized by the prior systemic or intrathecal administration of phentolamine (an alpha-blocker), but was unaffected by pretreatment with propranolol (a beta-blocker). The effect of intrathecal NE was significantly potentiated by prior administration of Lilly 51641 (a monoamine oxidase inhibitor) and protriptyline (a re-uptake inhibitor), and was not antagonized by the intrathecal administration of a non-specific vasodilator, papaverine. The antinociceptive effect of intrathecal NE showed tachyphylaxis following repeated injections. No cross-tolerance between intrathecal NE and morphine was observed, suggesting that the spinal action of morphine is not mediated by spinal noradrenergic terminals. Importantly, naloxone had no effect on the intrathecal NE effect. The present data provide further evidence for the modulatory role of a spinal noradrenergic system on the spinal processing of nociceptive transmission.

Animals↗
PubMed1975

Tricyclic antidepressive drugs and dopamine-sensitive adenylate cyclase from rat brain striatum.

Tricyclic antidepressant drugs were examined as inhibitors of dopamine-sensitive adenylate cyclase in a cell-free homogenate of rat brain striatum. Amitriptyline (Ki 0.17 muM) and doxepin (Ki 0.24 muM) were found to be potent inhibitors of dopamine-sensitive adenylate cyclase, chlorimipramine (Ki 0.59 muM) and nortriptyline (Ki 0.50 muM) were moderate inhibitors and imipramine, desmethylimipramine, protriptyline and melitracene were weak inhibitors with Ki values higher than 1 muM.

Adenylyl Cyclase Inhibitors↗
PubMed1976

Evaluation of the antinociceptive effects of 4, alpha-dimethyl-m-tyramine (H 77/77) in the rat.

4, alpha-Dimethyl-m-tyramine (H 77/77) has been shown to induce dose dependently antinociceptive activity against 3 parameters: (1) the motor (M), (2) the vocalisation during stimulation (V) and (3) the vocalisation after withdrawal of stimulation (VA) responses. The effect of H 77/77 upon the V and VA pain responses was abolished or reduced by prior treatment with phenoxybenzamine, chlorpromazine, H 44/68, FLA 63, reserpine and protriptyline, and was potentiated by atropine sulphate. It is suggested that H 77/77 may exert is inhibitory effect on painful stimulation predominantly by inhibiting spinal sensory input.

Amines↗
PubMed1980

High affinity binding of tricyclic antidepressants to histamine H1-receptors: fact and artifact.

Six tricyclic antidepressants were tested for their ability to inhibit the binding of the histamine H1-receptor antagonist [3H]pyrilamine to membrane fractions from whole rat brain. Calculated inhibition constants (Ki) for the antidepressants were in the range of 2.6 x 10(-11) to 2.3 x 10(-7) M and correlated very well with their equilibrium dissociation constants derived from biological assays of the H1-receptor. Increasing the concentration of receptors present in the binding assay resulted in an overestimation of the calculated Ki's for doxepin, amitriptyline, and nortriptyline, but not for the lower affinity compounds of the series, imipramine, protriptyline, and desipramine. These results indicate: (1) the importance of receptor concentration in determining the potency of compounds which competitively inhibit, with very high affinity, the binding of a radioactively labeled ligand; (2) the need to correlate binding data with biological data.

Animals↗
PubMed1980

Alcohol intake and ethanol intoxication in the rate: effect of a 6-OHDA-induced lesion of the ascending noradrenaline pathways.

The ascending noradrenaline (NA) pathways were lesioned by injecting 6-hydroxydopamine (6-OHDA) 16 micrograms/4 microliters bilaterally into the posterior mesencephalon in male Long Evans rats. Another group of rats was pretreated with protriptyline (25 mg/kg), a NA uptake blocking agent, 15 min before they received the intracerebral injections of 6-OHDA. The controls received the vehicle only. Spectrofluorimetric determination of the catecholamine concentrations in various parts of the brain revealed a marked degeneration of the ascending NA systems in the group receiving 6-OHDA. Unexpectedly, the DA systems were also affected by the 6-OHDA treatments. Three weeks after the operation the 6-OHDA group showed a transient increase in ethanol intake. In the tilting-plane test, ethanol (2 g/kg. i.p.) impaired the performance of the 6-OHDA-treated rats significantly more than that of the controls. In contrast, the hypothermic effect of ethanol (4 g/kg, i.p.) was significantly smaller in the lesioned rats. Furthermore, the catecholamine levels in various parts of the brain could be significantly correlated with both the extent of ethanol intoxication and the hypothermia. However, the duration of ethanol-induced narcosis (4 g/kg, i.p.) was affected by the present treatments. These results give further support for the view that the central NA neurons are important in the control of ethanol intake, and that they are involved in the expression of the acute effects of ethanol administration.

Alcohol Drinking↗
PubMed1989

Acute and long-term regulation of brain alpha 2-adrenoceptors after manipulation of noradrenergic transmission in the rat.

The specific binding of [3H]clonidine (KD and Bmax) to rat brain membranes was used as a biochemical index to directly evaluate alpha 2-adrenoceptor changes after manipulation of synaptic noradrenaline (NA) pools or stimulation or blockade of the receptor. Acute (2 h) and prolonged (7 days) inhibition of NA synthesis with alpha-methyl-p-tyrosine (150 mg/kg) or acute (2 h) and chronic (14 days) treatment with reserpine (0.1-0.5 mg/kg) reduced the NA content by 15-90%, which also resulted in marked reductions (35-55%) of the KD values for [3H]clonidine in all brain regions studied. In contrast to alpha-methyl-p-tyrosine, chronic reserpine treatment did not alter the Bmax values for [3H]clonidine or [3H]UK 14304 in any brain region. In the hypothalamus and cerebral cortex, acute (2 h) and chronic (7-14 days) treatment with the monoamine oxidase (MAO) inhibitors clorgyline (1 mg/kg) or tranylcypromine (5 mg/kg) increased the content of NA by 6-100%, which led to marked reductions (20-50%) of Bmax without altering the KD values for [3H]clonidine. Similarly, prolonged (21 days) inhibition of NA neuronal uptake with cocaine or protriptyline (10 mg/kg) also resulted in decreases in Bmax (20-25%) with no alterations in KD in the hypothalamus. In various brain regions, chronic (14 days) but not short-term (1 day) treatment with clonidine (0.1 mg/kg) or yohimbine (10 mg/kg) resulted in decreases (30-40%) and increases (15-20%), respectively, in Bmax without altering the KD values for [3H]clonidine. The results indicate that drugs which deplete endogenous NA up-regulate alpha 2-adrenoceptors (increased affinity of [3H]clonidine binding sites) while drugs which increase the intraneuronal and/or synaptic NA pools down-regulate the receptors (decreased number of [3H]clonidine binding sites). These adaptive receptor changes appear to be dependent on NA availability.

Adrenergic alpha-Agonists↗
PubMed1995

4-Aminopyridine-induced phasic contractions in rat caudal epididymis are mediated through release of noradrenaline.

4-Aminopyridine, a K+ channel blocker, evoked phasic contractions in the caudal duct of the rat epididymis. The 4-aminopyridine-induced contractile response was either inhibited or prevented by the alpha 1-adrenoceptor antagonists, prazosin (IC50 = 2.7 nM) and benoxathian (IC50 = 14.6 nM). Blockers (1 microM) of alpha 2-adrenoceptors and purinoceptors but not of beta-adrenoceptors or muscarinic receptors caused a small but statistically significant reduction of the 4-aminopyridine-induced response. 4-Aminopyridine lost its ability to induce contractions after noradrenergic nerves had been destroyed by 6-hydroxydopamine. In addition, protriptyline and xylamine, blockers of noradrenaline uptake, also inhibited the 4-aminopyridine-induced contractile response. However, other putative K+ channel blockers (tetraethylammonium ion, quinine, quinidine and glibenclamide) did not cause the muscle to contract. These findings demonstrate that the 4-aminopyridine-induced release of noradrenaline and adenosine 5'-triphosphate as co-transmitters results from membrane depolarization due to 4-aminopyridine blockade of K+ channels in noradrenergic nerve terminals. The 4-aminopyridine-sensitive K+ channels might thus play a physiological role in regulating the nerve membrane potential and neurotransmission in the rat caudal epididymis.

4-Aminopyridine↗
PubMed1996

Effect of 5,7-dihydroxytryptamine on audiogenic seizures in genetically epilepsy-prone rats.

To further assess the role of 5-HT in the modulation of audiogenic seizures (AGS) in the Genetically Epilepsy-Prone Rat (GEPR), changes in AGS severity after widespread chronic depletion of brain 5-HT by intracerebroventricular administration of 5,7-dihydroxytryptamine (5,7-DHT) were examined in moderate seizure GEPRs (GEPR-3s). Following treatment with 5,7-DHT (150 micrograms/30 microliters), a significant increase in seizure severity was observed at 2, 3 and 4 weeks as compared to vehicle-injected controls. The increase in seizure severity was evidenced by a significant increase in the incidence of tonic convulsions in 5,7-DHT treated animals (53% in treated animals compared to 0% in vehicle treated controls) over the testing period. Interestingly, the latency to wild running was increased in 5,7-DHT treated GEPRs, suggesting that depletion of brain 5-HT may slow initiation of AGS. Neurochemical analysis revealed marked depletion of 5-HT in the cortex (-96%), hippocampus (-94%), thalamus (-80%), hypothalamus (-62%), midbrain (-51%) and pons-medulla (-52%) in animals that received 5,7-DHT. However, no significant reductions in brain norepinephrine content were observed in any of the regions assayed due to the pretreatment of all animals with protriptyline. The present findings lend further support for an inhibitory action of brain 5-HT on audiogenic seizures in GEPRs.

5,7-Dihydroxytryptamine↗
PubMed1996

[3H]nisoxetine--a radioligand for noradrenaline reuptake sites: correlation with inhibition of [3H]noradrenaline uptake and effect of DSP-4 lesioning and antidepressant treatments.

Nisoxetine is a potent and selective inhibitor of noradrenaline uptake into noradrenergic neurones. [3H]Nisoxetine binding to rat frontal cortical membranes was of high affinity. The binding data of both competition and saturation studies fitted a single site binding model. [3H]Nisoxetine binding was potently inhibited by the selective noradrenaline uptake inhibitors desipramine and protriptyline. In addition, a very good correlation was obtained between the ability of 25 monoamine reuptake inhibitors and related compounds both to inhibit [3H]nisoxetine binding and to inhibit [3H]noradrenaline uptake in rat frontal cortex. DSP-4 (10-100 mg/kg, i.p.) dose-dependently depleted cortical noradrenaline concentrations (51-100%), with no significant effects on 5-HT and dopamine. These depletions, which were used as a marker of loss of noradrenergic nerve terminals, were associated with a dose-dependent decrease in the number of [3H]nisoxetine binding sites (20-97%) with no change in binding affinity. Furthermore, a good correlation was obtained between cortical noradrenaline concentrations and the number of [3H]nisoxetine binding sites. These data support the view that [3H]nisoxetine binds to a single population of homogeneous sites associated with the noradrenaline transporter complex. Using this ligand, the effects of repeated administration of both antidepressant drugs with a range of pharmacological actions and of electroconvulsive shock on noradrenaline reuptake sites were examined. The number and affinity of [3H]nisoxetine binding sites were unaltered by all treatments. It is unlikely, therefore, that antidepressant therapy would produce adaptive changes in noradrenaline uptake sites.

Animals↗
PubMed1985

The acute effects of antidepressant drugs on the performance of conditioned avoidance behavior in rats.

The effects of acute administration of 10 different antidepressant drugs were examined on the performance of a two-way conditioned avoidance response in rats. The antidepressant drugs impaired avoidance behavior by decreasing avoidance responding and increasing the number of escape failures. The order of effectiveness for increasing overall response latency at a common dose of 10 mg/kg was: desipramine, maprotiline, protriptyline, (+) oxaprotiline, nortriptyline, imipramine, amitriptyline, (-) oxaprotiline, fluoxetine, and chlorimipramine. Avoidance behavior was impaired most by those antidepressant drugs that are also potent inhibitors of norepinephrine uptake.

Animals↗
PubMed1993

Determination of clozapine and desmethylclozapine in human plasma by high-performance liquid chromatography with ultraviolet detection.

A method using reversed-phase high-performance liquid chromatography for the simultaneous determination of clozapine and its desmethyl metabolite in human plasma has been established. Clozapine and N-desmethylclozapine were extracted with n-hexane-isoamyl alcohol (98.5:1.5, v/v). Protriptyline served as the internal standard. The limits of detection for clozapine and desmethylclozapine are 2 and 1 ng/ml, respectively. The sensitivity and precision of this method can be utilized for pharmacokinetic studies and therapeutic drug monitoring regimens.

Adult↗
PubMedDate not supplied

The pharmacokinetics of tricyclic antidepressant drugs in the elderly.

Antidepressants, especially tricyclic agents (TCAs), are increasingly used in geriatric patients since depression is a common mood disorder in the elderly and the size of elderly population is increasing. Notwithstanding the importance of kinetics to better use of drugs, its study in the elderly (regarding TCAs) is not sufficiently developed. The present paper briefly reviews the available data on amitriptyline, nortriptyline, protriptyline, imipramine, desipramine and clomipramine kinetics in the elderly.

Aged↗