Disease relevance of Tocris-1001

• Combined pretreatment (i.p. administration) with the ganglionic and muscarinic blocking agents chlorisondamine (5 mg/kg of body weight) and atropine (1 mg/kg) blocked the increase in levels of proenkephalin A mRNA seen in the rat adrenal medulla following insulin hypoglycemia [1].
• Following ganglionic blockade with chlorisondamine, NTS lesions still elicited hypertension, and the magnitude of the hypertension was not different from that observed in rats not treated with chlorisondamine [2].
• Autonomic (largely sympathetic) influence on home-cage blood pressure, inferred from ganglion blockade with chlorisondamine, also did not differ between groups after 10 weeks of stress [3].
• The relatively non-subtype-specific channel-blocking nicotinic antagonists chlorisondamine and mecamylamine each inhibited the development of form-deprivation myopia but with complex multiphasic dose responses [4].
• Chlorisondamine but not mecamylamine also affected nongoggled eyes, inhibiting growth and shifting refraction toward hyperopia, but chlorisondamine also induced degenerative changes to the retinal pigment epithelium (RPE) [4].

Psychiatry related information on Tocris-1001

• When exposed to the social interaction test, neither restraint nor chlorisondamine affected social interaction, locomotion, or rearings [5].
• When chlorisondamine was used as a ganglionic blocker (2.5 mg.kg-1, IV), the fall in CVP at 10 mm Hg negative pressure was greater for the NT group while the fall in the initial systemic arterial pressure was more for the T group [6].
• Inhibition of the protein synthesis had no effect, ganglionic blockade by chlorisondamine on the other hand abolished the rhythm in the motor activity, subacute treatment with reserpine differently affected motor activity in both photo-periods, depending on the time of drug application within 24 hr of a day [7].

High impact information on Tocris-1001

• The ganglionic blocker chlorisondamine, inhibits ACTH release during both phases of the response to ether by 40-60% when used alone, and by 100% when administered with anti-CRF antibody [8].
• Subcutaneous administration of chlorisondamine caused a significantly greater reduction of arterial blood pressure in sodium-depleted rats than it did in normal rats [9].
• To block neural transmission at sympathetic ganglia, chlorisondamine (3.0 mg/kg) was injected intraperitoneally 60 min before IL-1 infusion [10].
• Treatment with chlorisondamine, which blocks synaptic transmission in sympathetic ganglia, produces a significant increase in SV levels in the SCG after 7 d of treatment [11].
• In brain and sympathetic nerve, stimulation of transcription was more modest, and reserpine responses were only incompletely blocked by chlorisondamine or catestatin, perhaps because of limited blood-brain barrier penetration by these cationic antagonists [12].

Chemical compound and disease context of Tocris-1001

• The results of this study showed that combined nicotinic and muscarinic ganglion blockade with chlorisondamine and atropine did not decrease the amount of norepinephrine-produced depression of transmission [13].
• This result indicates that in an acute model of hypertension, where baroreflex mechanisms have likely withdrawn sympathetic tone, neither clonidine nor chlorisondamine had nonspecific antihypertensive effects [14].
• Administration of a single dose of the muscarinic agonist, oxotremorine, also resulted in a hyperglycemia that was blocked by chlorisondamine [15].
• Pretreatment with the ganglionic blocking agent Ecolid, alpha-adrenoceptor antagonist phenoxybenzamine or the monoamine depleting agent reserpine blocked this effect without affecting intravenous vasopressin-induced hypertension [16].
• The PACAP-27-induced tachycardia was unaffected by chlorisondamine, but was virtually abolished by propranolol [17].

Biological context of Tocris-1001

• Direct nicotinic stimulation of chromaffin cells caused catecholamine release and transgene transcription, each of which was nearly completely blocked by chlorisondamine [12].
• After pretreatment with chlorisondamine (5 mg/kg IP) or prazosin (5 mg/kg IP) to inhibit autonomic ganglionic or alpha 1-adrenoceptor functions, respectively, ZnDPBG did not affect arterial pressure or heart rate [18].
• Whereas the antagonists dihydro-beta-erythroidine (IC50 of 3-6 nM) and methyllycaconitine (IC50 of 40-135 nM) were not selective between high- and low-sensitivity alpha4beta2, chlorisondamine, mecamylamine, and d-tubocurarine were, respectively, 100-, 8-, and 5-fold selective for the alpha4beta2 subform with low sensitivity to acetylcholine [19].
• Ganglionic blockade (chlorisondamine 2 mg/kg i.v.) diminished mean arterial responses without altering peptide effects on renal circulation [20].
• As before, this up-regulation was neither mimicked nor blocked by chlorisondamine pretreatment (10 mg kg-1, s.c., given twice), despite persistent blockade of acute locomotor responses to nicotine.(ABSTRACT TRUNCATED AT 250 WORDS)[21]

Anatomical context of Tocris-1001

• The role of the sympathetic nervous system on morphine-mediated effects was investigated by using the ganglionic blocker chlorisondamine [22].
• Here we show that in vivo blockade of the autonomic nervous system by intraperitoneal injection of the nicotinic receptor antagonist chlorisondamine leads to complete abrogation of these stress-induced alterations in AM activity [23].
• 3. The response to pylorus ligation in innervated rats was blocked by atropine and chlorisondamine but not by metiamide [24].
• In contrast, no recovery was seen in synaptosomes prepared from rats pretreated with chlorisondamine (10 mg kg-1, s.c.) in vivo [25].
• This beta-endorphin-induced increase in plasma catecholamine concentration is dose-dependent, inhibited by naloxone and blocked by bilateral adrenal gland denervation or ganglionic blockade with chlorisondamine [26].

Associations of Tocris-1001 with other chemical compounds

• These peripheral effects of CRF were not prevented by blockade of autonomic efferents with bretylium or chlorisondamine [27].
• Peripheral injections of the autonomic ganglionic blockers hexamethonium (10 mg/kg) or chlorisondamine (3 mg/kg) slightly attenuated the magnitude of CRF-enhanced startle, suggesting a partial role of peripheral sympathetic activation [28].
• Pretreatment with the ganglionic blocker chlorisondamine completely prevents the CRF-induced rises in plasma glucose, epinephrine, and norepinephrine [29].
• Serum levels of PAM activity were unaltered after hypophysectomy, adrenalectomy, sialectomy, or castration, but rose after thyroidectomy and declined after treatment with the ganglionic blocker chlorisondamine or phenoxybenzamine [30].
• In this work, rat brains were collected after intracranial injection of chlorisondamine or intraperitoneal injection of cocaine and snap frozen [31].

Gene context of Tocris-1001

• CRF inhibited the evoked response of these units in a dose-dependent manner with an ED50 of 2.3-7 nmol/kg i.v. Neither naloxone nor chlorisondamine pretreatment prevented the inhibitory actions of CRF [32].
• Pretreatment with chlorisondamine, a ganglionic blocking agent, inhibited the Il-6 responses, while it had little influence on the TNF responses [33].
• Chlorisondamine, administered at a dose which completely blocks ganglion transmission, blocked the increase in TH activity [34].
• Blockade of the sympathetic transmission by chlorisondamine prevented the inhibitory effect of morphine on TNF-alpha production [35].
• The suppressive effect of urocortin was abolished by pretreatment with a ganglionic blocking agent (chlorisondamine) or a beta-adrenergic receptor antagonist (propranolol), but not by adrenalectomy [36].

Analytical, diagnostic and therapeutic context of Tocris-1001

• Neither chlorisondamine nor adrenalectomy alters morphine's suppressive effect on splenic natural killer cell cytotoxicity [37].
• Intraventricular injections of chlorisondamine have a specific and unusually persistent nicotine-blocking action, the mechanism of which requires further investigation [38].
• In intact rats, SK&F 87516 produced dose-related bradycardic effects that were inhibited (50%) by idazoxan, methylatropine or bilateral vagotomy and abolished by chlorisondamine or pithing [39].
• In keeping with past reports regarding the effects of restraint and ganglionic blockade upon anxiety, we have also measured the behavioural effects of restraint and/or chlorisondamine in two animal models of anxiety, the elevated plus-maze and the social interaction test [5].
• Intravenous injections of chlorisondamine (a ganglion blocker) blocked the increase in HR elicited by injections of 1.5 pmole of NE into the IML.(ABSTRACT TRUNCATED AT 250 WORDS)[40]

References