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Biomedical subjects

C Y Chiou

Publications and source records attributed to C Y Chiou.

At least 37 records · Page 2Linked to original sources
PubMed1979

Effects of diethylcholine in two animal models of Parkinsonism tremors.

(2-Hydroxyethyl) methyldiethylammonium iodide (diethylcholine; DEC) was tested against trihexyphenidyl for its ability to block tremors in two animal models of Parkinsonism tremors. Both DEC (75 mg/kg) and trihexyphenidyl (10 mg/kg) antagonized physostigmine tremors in mice. Both drugs also blocked tremors in rats which received intracaudate injections of carbachol. DEC was more efficacious than trihexyphenidyl in the rat model. No dose-related inhibition of tremors was seen for trihexyphenidyl (5--20 mg/kg) but inhibition by DEC was dose-related (25--50 mg/kg). The ED50 for tremor inhibition in the rat model by DEC was 33 mg/kg. DEC was also shown to cross the blood-brain barrier in mice. The probable mechanism of action of DEC is discussed.

Animals↗
PubMed1978

Treatment of neuroblastoma in mice with bromoacetylcholine and bromoacetate.

Bromoacetylcholine (30 mg/kg intratumor one to three times per day) and bromoacetate (12 mg/kg intratumor two times per day) inhibited neuroblastoma in A/J mice efficiently and prolonged the lifespan of these animals at least 200%. Since the neuroblastoma-inoculated A/J mice are considered to be comparable to human neuroblastoma, the cytolytic action of bromoacetylcholine and bromoacetate on murine neuroblastoma warrants further studies on patients. The fact that these tumors were cured in adult mice is very important because older children and adults with neuroblastoma have the poorest prognosis.

Acetates↗
PubMed1978

Pharmacological studies on N-demethylated carbachol.

In attempts to find a drug more active than pilocarpine, the tertiary nitrogen derivative of carbachol, N-demethylated carbachol, was synthetized and tested on several autonomic nervous system preparations. N-Demethylated carbachol was active at muscarinic and nicotinic sites in vivo and in vitro. In superfusion studies, N-demethylated carbachol contracted the smooth muscle of the guinea pig ileum as well as skeletal muscles of frog recus abdominis and chick biventer cervicis. N-Demethylated carbachol decreased blood pressure in the rat, with an ED50 ("/- SEM) of 4.82 +/- 0.78 mg/kg. After close arterial injection to the cat superior cervical ganglion, N-demethylated carbachol elicited contractions of the nictitating membrane (ED50 of 1.68 +/- 0.24 mg/kg) that were not significantly affected by atropine. N-D-methylated carbachol stimulated salivation in dog Wharton duct preparations with an ED50 of 2.55 +/- 0.81 mg/kg. In contrast, pilocarpine had no effects on skeletal muscles in vitro, produced ganglionic effects blocked by atropine, had a prominent effect on salivation, and tended to elevate blood pressure.

Animals↗
PubMed1978

Cytolysis of rat glioma cells in vitro by autonomic drugs.

The results of glioma chemotherapy obtained so far have been rather disappointing. New attempts have been made to kill glioma cells with autonomic drugs. Experiments were done with rat C-6 glioma cells in the cell culture. Among all cholinergic blockers tested, only the irreversible cholinergic blockers such as bromoacetylcholine (BrACh), iodoacetylcholine and alphabungarotoxin were effective to inhibit glioma cells (with 50% cytolytic doses of 6.7 x 10(-6)M, 3.0 x 10(-6)M and 7.4 x 10(-5)M respectively). It is interesting to note that the hydrolytic product of BrACh, bromoacetate, was as potent as BrACh to inhibit glioma cells. Most of the adrenergic blockers, both reversible and irreversible ones, showed no cytolytic activity on glioma cells with concentrations up to 1.0 x 10(-4)M except phentolamine and propranolol which showed weak cytolytic activities. It is interesting to note, on the other hand, that 6-hydroxydopamine (an adrenergic neuron degenerating agent) and 5,6-dihydroxytryptamine (a serotonergic neuron degenerating agent) also showed mild cytolytic effects on glioma cells with 50% cytolytic doses of 5.0 x 10(-5)M and 5.3 x 10(-5)M, respectively.

Acetylcholine↗
PubMed1977

Cytolysis of neuroblastoma cells in vitro and treatment of neuronal tumors in vivo with bromoacetylcholine.

The effect of bromoacetylcholine on mouse neuroblastoma C-1300 was investigated in cell culture as well as in A/J mice. In vitro, bromoacetylcholine (1 X 10(-5) M) was a potent cytolytic agent and produced an additive effect in combination with vincristine (3 X 10(-9) M). Since the choline acetyltransferase inhibitor, dimethylaminoethyl chloroacetate, does not inhibit neuroblastoma efficiently in vitro, the potent cytolytic action of bromoacetylcholine is probably not due to its choline acetyltransferase inhibitory action. Furthermore, the neuroblastoma inhibitory effect of bromoacetylcholine was not affected by atropine. Therefore, the inhibitory action is not related to the interaction of bromoacetylcholine with muscarinic receptors either. In in vivo experiments, 1, 10, or 30 mg/kg of bromoacetylcholine was injected directly into the tumors three times daily for 6 weeks. Bromoacetylcholine at 10 and 30 mg/kg gave significant protection of A/J mice from the death induced by neuroblastoma inoculation, and the lifespan was prolonged significantly with these bromoacetylcholine treatments.

Acetylcholine↗
PubMed1976

On GABA function and physiology in the pineal gland.

Pineal gamma-aminobutyric acid (GABA) content and glutamic acid decarboxylase (GAD) activity were found not to be influenced by environmental light, catecholamines, sympathetic innervation, or input via the pineal stalk. The observation that GAD activity did not disappear after pineal stalk section, ganglionectomy, or 48 h of organ culture leads us to suggest that GAD activity is not located in nerve processes entering the pineal gland. Treatment in organ culture with an inhibitor of protein synthesis did not greatly influence the slow rate of decrease of GAD activity. This finding is consistent with the conclusion that GAD turnover is slow. Treatment of denervated glands or glands containing functional sympathetic nerve structures with GABA, amino-oxyacetic acid (AOAA) or bicuculline in organ culture did not alter unstimulated levels, or significantly block the adrenergic stimulation of the activity of pineal serotonin N-acetyl transferase (NAT). It is clear from our studies that GABA does not influence or modulate the adrenergic regulation of.pineal NAT activity, and that GABA content and synthesis are not regulated by an adrenergic mechanism. The role of GABA in the pineal gland remains to be discovered.

Acetylcholinesterase↗
PubMed1976

In vivo effects of some tertiary alkylaminoethyl esters with choline acetyltransferase inhibitory properties.

The tertiary nitrogen derivatives of two choline esters, chloroacetylcholine and acrylcholine, known to inhibit choline acetyltransferase (ChAc) in vitro, were tested for their effects in the whole animal, including peripheral and central cholinergic systems. These esters are N,N-dimethylaminoethyl chloroacetate (Cl-DMA) and N,N-dimethylaminoethyl acrylate (acryl-DMA). The peripheral preparations studied included a neuromuscular junction, a sympathetic ganglion and a postganglionic parasympathetic exocrine preparation. Both Cl-DMA and acryl-DMA blocked responses in these preparations when injected intravenously. The LD50 values for Cl-DMA and acryl-DMA were 640 mg/kg and 183 mg/kg, respectively. Cl-DMA and acryl-DMA were also able to inhibit brain ChAc when injected intravenously by 32% and 18.5%, respectively. The brain levels of acetylcholine (ACh) were significantly reduced by about 25% with Cl-DMA but not significantly with acryl-DMA when the animals were forced to exercise after injection. It is obvious that ChAc inhibition is not effective in decreasing ACh levels significantly under normal conditions.

Acetylcholine↗
PubMed1976

Chemistry and biological activities of N,N-dimethylaminoethyl acrylate, a choline acetyltransferase inhibitor.

N,N-Dimethylaminoethyl acrylate (acryl-DMA) was synthesized as a tertiary nitrogen choline acetyltransferase (ChAc) inhibitor which would be able to penetrate biological membranes to inhibit ChAc in the nerve terminal. The synthesis from dimethylaminoethanol and acrylyl chloride was described and the hydration with times in an aqueous medium measured by NMR spectroscopy was presented. The autohydrolysis in water was found to be 1.75 x 10(-8) mol/min at pH 7.4 and 5.0 mM concentration. The enzymatic hydrolysis was unaffected by cholinesterases. Acryl-DMA was capable of inhibiting ChAc extracted from rat brain with I50 of 5.02 x 10(-4) M. The inhibition was reversible and displayed uncompetitive kinetics with respect to both substrates, choline and acetyl-CoA. Neither the hydrolysis nor the hydration products of acryl-DMA could inhibit ChAc. Although acryl-DMA was hydrated rapidly and completely within 1 hr at high pH (9.0), the time course of inhibition ability of acryl-DMA in aqueous medium at physiological pH was found to decrease rather slowly and by 36% in 1 hr, indicating that acryl-DMA can survive from hydration at physiological pH. Acryl-DMA was also tested for its ability to block electrically induced muscle contractions in both isolated skeletal and smooth nerve-muscle preparations. The ED50's obtained were less than 5 x 10(-4) M in both cases.

Acetyltransferases↗
PubMed1976

Electrophysiological studies of 6-(N,N-diethylamino)-Hexyl-3,4,5,-Trimethoxybenzoate on ventricular muscle and conduction system.

The agent, 6-(N,N-diethylamino)-hexyl- 3, 4, 5,-Trimethoxybenzoate (TMB-6) which relaxes smooth and skeletal muscle by interfering with intracellular Ca ++ availability was tested for its electrophysiological effects on canine cardiac Purkinje fibres and feline papillary muscles. In both tissues the drug causes a decrease in resting membrane potential and action potential amplitude as well as spontaneous rate in Purkinje fibres, and an increase in stimulus needed to reach threshold. The minimum effective dose for both tissues was similar at 7.32 x 10-5 M. The drug effects were reversible in both tissues upon removal of the TMB-6. The Ca++ -dependent action potentials of canine cardiac Purkinje fibres were also inhibited by TMB-6 at dose range of 7.32 x 10-5 -24.4 x 10-5 M. Because of its electro physiological effects of threshold, automaticity and "slow response" action potentials and its reversibility, TMB-6 could become a useful antiarrhythmic drug.

Action Potentials↗
PubMed1976

Pharmacological studies of N,N-dimethylaminoethyl chloroacetate and N,N-dimethylaminoethyl acrylate as inhibitors of choline acetyltransferase in isolated skeletal and smooth muscle preparations.

Two tertiary amine esters, N,N-dimethylaminoethyl chloroacetate (Cl-DMA) and N,N-dimethylaminoethyl acrylate (acryl-DMA), which have recently been shown to be inhibitors of choline acetyltransferase (ChAc) were investigated to determine their actions in isolated skeletal and smooth muscle preparations. Both compounds caused neuromuscular blockade in indirectly stimulated nerve-muscle preparations (ED50 values of Cl-DMA were 6.9 -42.0 X 10(-4) M and those of acryl-DMA were 1.2-5.8 X 10(-4) M). The blockade was completely or partially reversible after drug washout. A comparison of the ED50 values for neuromuscular blockade with the ID50 values for ChAc inhibition suggested that the acryl-DMA compound might not cause neuromuscular blockade via ChAc inhibition because the potency ratios (ED50/ID50) of Cl-DMA were higher than 1, whereas those of acryl-DMA were equal to or lower than 1. This was borne out by further experiments on isolated neuromuscular preparations which showed that the site of action for acryl-DMA was post-junctional, whereas that for Cl-DMA was prejunctional. In addition, the weak stimulating properties of Cl-DMA and acryl-DMA were investigated in isolated skeletal and smooth muscle. Cl-DMA was shown to be a partial cholinergic agonist, whereas acryl-DMA was a nonspecific stimulant not involving cholinergic receptors. Although both Cl-DMA and acryl-DMA are inhibitors of ChAc, only Cl-DMA appears to have sufficient specificity for use as a possible ChAc inhibitor in vivo.

Acetates↗