摘要:

AbstractRecent in vivo and in vitro studies regarding the involvement of GABAergic systems in cardiovascular function have been reviewed and analyzed. It seems evident, from studies conducted with various GABA agonists and GABA antagonists, that activation of central GABAergic systems reduces sympathetic outflow from the hindbrain area of mammals, thereby producing bradycardia and hypotension. As GABA agonists can relax cerebral arteries, blood‐borne GABA might also play a role in cerebrovascular regulation. Further research concerning the mechanisms involved in GABA agonist‐induced cardiovascular responses could lead to the development of agents that might be effective in treating certain cardiovascular disorders of man, such as hypertension, cerebral atherosclerosis, migraine, and str

ISSN:0272-4391    

DOI:10.1002/ddr.430020602

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe effects of increasing doses of cibenzoline (‐2(2,2‐diphenylcyclopropyl)‐2‐imidazoline, Cipralan), a new compound with antiarrhythmic properties, on systemic hemodynamics and regional myocardial performance were studied in anesthetized pigs. Doses of 0.5–2.0 mg kg−1i.v. produced a 10–15% prolongation of the PP' interval, and a dose‐dependent increase (up to 60%) in QRS width, with only minor changes in PQ and ST length. Stroke volume decreased dose dependently (20–35%) immediately after drug administration, due to a decrease in myocardial contractility and an increase in systemic vascular resistance. Renal blood flow was unchanged, despite the decrease in cardiac output. Coronary blood flow decreased, while myocardial O2extraction was unchanged. Hence myocardial O2consumption decreased parallel to the decrease in flow, a consequence of the lowered myocardial O2demand. Studies with radioactively labeled microspheres revealed that the decrease in myocardial blood flow was equally distributed over the

ISSN:0272-4391    

DOI:10.1002/ddr.430020603

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe efficacy of a new eburnamenine derivative (RU 24722) on cerebral insufficiency was studied by evaluation of postischemic EEG recovery in the conscious gerbil. Ischemias of different durations were obtained by clamping both common carotids. This method required only brief anesthesia, thereby permitting the recording of EEG recovery in unanesthetized and unrestrained animals during the 24 hr following arterial occlusion. The EEG was analyzed by the Fast Fourier Transform. Mortality rate and clinical status were also evaluated. After a 5‐min ischemia the initial return of EEG was characterized by very high amplitude slow waves (1–2 Hz) and the EEG became normal 24 hr after ischemia. No mortality was observed. After a 10‐min ischemia the early recovery phase was characterized by a decrease in the power spectrum and a rebound of slow frequency waves after 2–4 hr. After 24 hr the EEG was not yet completely normal and 1 animal out of 10 died. A 15‐min ischemia killed 50% of the animals, and the EEGs of the survivors were abnormal even after 24 hr. Treatment with RU 24722 (10 mg/kg/s.c.) significantly improved the electrocortical recovery of gerbils submitted to a 10‐min ischemia. In this group the EEG was normalized 6 hr after ischemia in the same way as in the controls submitted to a 5‐min ischemia. These findings suggest that RU 24722 may have a therapeutic effect in cerebral

ISSN:0272-4391    

DOI:10.1002/ddr.430020604

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractAntiserotoninergic effects of maprotiline and its hydroxy derivative oxaprotiline (Ba 49802 B), two selective inhibitors of NA uptake, and clinically active antidepressants were investigated in several functional tests and also in in vivo3H‐spiperone binding assay in the rat. In some tests comparisons with amitriptyline, mianserin, and fluoxetine, which are antidepressants of different qualities, were also done. After single doses up to 30 mg/kg neither maprotiline nor oxaprotiline inhibited L‐5‐HTP‐induced head twitch in mice or tryptamineinduced paw clonus in the rat. Maprotiline, however, but not oxaprotiline, significantly reduced the hyperthermic response to LSD in rabbits and blocked to nearly 90% the3H‐spiperone labeled 5‐HT receptors in the rat frontal cortex at a dose of 30 mg/kg. Moreover, maprotiline also reduced the response of mice to L‐5‐HTP after daily administration of 25 mg/kg over 10 days. No change in the responsiveness of mice to L‐5‐HTP was observed after the same treatment with oxaprotiline. In agreement with other observations, mianserin and amitryptiline displayed clear‐cut antiserotoninergic effects, whereas fluoxetine potentiated the effects of tryptamine and LSD. The results of this study indicate that, although chemically closely related, maprotiline and oxaprotiline distinctly differ in respect to their action on 5‐HT receptors. Maprotiline exerts 5‐HT receptor blocking effects that appear to increase upon repetitive administration in mice. Oxaprotiline, by contrast, is devoid of them. Comparative experimental and clinical investigations of maprotiline and oxaprotiline may, therefore, provide a clue as to the importance of 5‐HT receptor blocking properties for antidepressant

ISSN:0272-4391    

DOI:10.1002/ddr.430020605

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe α‐adrenergic blocking properties of trazodone were assessed in spinal‐sectioned, vagotomized dogs. Both the inhibition by clonidine of the tachycardia produced by continuous cardiac accelerator nerve stimulation (presynaptic effect) and the vasopressor effects of clonidine (postsynaptic effect) were antagonized by trazodone and phentolamine in this model. The results indicate that although it is 12–18 times less potent on a weight basis, trazodone, like phentolamine, blocks presynaptic α‐adrenergic receptors on the cardiac nerves of anesthetized dogs. Trazodone, unlike imipramine, did not potentiate the positive inotropic responses elicited by exogenously administered norepinephrine. The latter observation supports the interpretation that trazodone altered positive chronotropic responses to cardiac accelerator nerve stimulation via presynaptic α‐receptor blockade rather than by either an interference with neuronal reuptake of norepinephrine or a heightening of ß‐adrenergic recep

ISSN:0272-4391    

DOI:10.1002/ddr.430020606

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThirteen known H1‐antagonists were studied in a series of pharmacological in vivo tests in rats. Antihistamine activity, oral absorption, and duration of action were determined in the compound 48/80 test. The dissociation between the activity in the compound 48/80 test and in the other tests was used as a measured of antihistaminic specificity. Properties common to several H1‐antagonists were: antimuscarinic (diphenhydramine, promethazine, mequitazine, azatadine, cyproheptadine, chlorphenriamine, clemastine, pyrilamine) and anti‐serotonin activity (mianserin, pizotifen, cyproheptadine, prometazine, diphenhydramine, pyrilamine). Sedative effects of H1‐antagonists were not detected by the pharmacological tests used here. Astemizole, ketotifen, and terfenadine were found to be very specific H1‐antagonists. For ketotifen and terfenadine, oral activity (1/5 and 1/25 of astemizole, respectively) and oral absorption (1/50 and 1/7 respectively) were poor, and the duration of action (4 and 6 hr, respectively) was relatively short. Astemizole was as potent orally as it was subcutaneously (ED50 = 0.11 mg/kg) and appeared to have a duration of action as long

ISSN:0272-4391    

DOI:10.1002/ddr.430020607

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe effects of local deposition of the topical anesthetic, lidocaine, and ganglionic blockade by hexamethonium were investigated in canine models of pharmacologic‐ and antigen‐induced bronchoconstriction. Control bronchopulmonary provocations, i.e., increases in pulmonary resistance (RL) and decreases in dynamic lung compliance (CDYN), were accomplished by aerosols of prostaglandin F2α(PGF2α) and histamine (HIST) in normal, pentobarbital‐anesthetized beagles. Pretreatment with an aerosol of lidocaine (2%, 30 breaths) significantly inhibited PGF2α‐ and HIST‐induced changes in RLby 43.9 ± 6.5% and 58.0 ± 10.9%, respectively, and significantly reduced CDYNchanges due to an aerosol challenge with HIST by 43.6 ± 9.2%. An i.v. infusion of hexamethonium (10 mg/kg) significantly inhibited PGF2α‐ induced changes in RL(36.5 ± 10.4%), while inhibiting changes in both RLand CDYNproduced by HIST (57.8 ± 7.5% and 63.1 ± 6.5%, respectively). InAscaris‐sensitive animals, neither lidocaine nor hexamethonium had any statistically significant effect on the bronchopulmonary responses to antigen challenge. These results suggest that a portion of the bronchoconstrictive response to PGF2αand HIST in dogs may involve an indirect, vagal‐mediated reflex, which is sensitive to lidocaine at the afferent cholinergic pathway and to hexamethonium at the ganglion. In antigen‐induced bronchoconstriction, these reflex pathways

ISSN:0272-4391    

DOI:10.1002/ddr.430020608

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe injection of air into the peritoneal cavity of rats produces reliable and quantifiable behavioral responses. These responses are blocked by compounds known to have analgesic properties, including opioid agonists, opioid agonist‐antagonists, cyclo‐oxygenase inhibitors, and amine potentiators. However, psychotropic agents were generally inactive at reasonable doses. The ability of this assay to identify a wide spectrum of analgesic agents in rats was superior to the hot plate, warm plate, and tail immersion ass

ISSN:0272-4391    

DOI:10.1002/ddr.430020609

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractWHR‐1370A in the rat reduces volume (ED50 = 1.3 mg/kg p.o.) acidity (1.8 p.o.), and pepsin (2.8 p.o.) in the 4‐hr pylorus ligation model, delays gastric emptying (0.75 p.o.), and protects against the development of stress (18‐hr restraint)‐, indomethanic‐, aspirin‐, reserpine‐, and cysteamine‐induced ulcers (ED50s: 10.0 s.c., .65 p.o., 0.59 p.o., 3.0 p.o., and 8.0 s.c., respectively); also WHR‐1370A can completely suppress the cysteamine‐induced rise in serum gastrin. In the pylorus‐ligated rat, the activity of WHR‐1370A is not appreciably altered by methysergide, pimozide, propranolol, corynanthine, or phentolamine but is significantly and competitively antagonized by yohimbine. The pharmacological basis of WHR‐1370A probably can be attributed to an alpha‐2‐mediated inhibition of acetylcholine r

ISSN:0272-4391    

DOI:10.1002/ddr.430020610

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430020611

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY