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Biomedical subjects

M S Dar

Publications and source records attributed to M S Dar.

At least 55 records · Page 3Linked to original sources
PubMed1985

GABA mediation of the central effects of acute and chronic ethanol in mice.

In acute ethanol studies aminooxyacetic acid (AOAA) alone produced marked hypothermia although a test dose of ethanol was able to produce a further drop in body temperature in AOAA treated mice. Even though tolerance to ethanol-induced hypothermia was present in ethanol-dependent mice, AOAA administration was able to produce a further decrease in body temperature. Bicuculline potentiated ethanol-induced hypothermia in the acute studies but the tolerance to hypothermia which had developed in ethanol-dependent mice prevented the bicuculline-induced potentiation of ethanol hypothermia. AOAA markedly potentiated acute ethanol-induced motor incoordination whereas bicuculline had no effect. Although partial tolerance had developed to ethanol-induced motor incoordination in dependent mice, AOAA potentiated, whereas a lower dose of bicuculline antagonized, motor incoordination. In the acute studies ethanol had a biphasic effect on AOAA-induced GABA accumulation in the hypothalamus and corpus striatum: low doses prevented and a slightly higher dose was without effect on GABA accumulation. Ethanol-dependent mice were unable to respond to an AOAA-induced increase in GABA accumulation although basal levels of GABA were unaffected by chronic ethanol ingestion. The results show that brain GABA or GABA-mediated central mechanisms may be involved in the mediation of ethanol-induced motor incoordination but not hypothermia.

Alcoholism↗
PubMed1985

The enzymatic systems involved in the mammalian metabolism of methylamine.

The metabolism of methylamine has been investigated in the rat in order to elucidate the role of monoamine oxidase (MAO; EC 1.4.3.4) and intestinal bacteria in the metabolism of the compound. In a series of experiments in which short- and long-acting inhibitors of MAO were administered either alone or in combination prior to methyl-[14C]amine hydrochloride injection, the excretion of radioactivity in the expired air and the urine was examined to indirectly assess the role of MAO in the metabolism of methylamine. The data presented provide indirect evidence to demonstrate that the effect of iproniazid, an inhibitor of methylamine oxidation, is mediated through enzyme systems separate from MAO systems which have been invoked as major contributors to metabolism of methylamine by other investigators. The bacterial oxidation of methylamine in the intestine plays a minor role in the overall metabolism of the compound.

Animals↗
PubMed1985

Effect of chronic ethanol administration on arterial baroreceptor function and pressor and depressor responsiveness in rats.

The effect of chronic ethanol administration on arterial baroreflexes was investigated in rats. Comparison of the results with those obtained from rats kept on an isocaloric control diet revealed that chronic ethanol had a differential action on baroreflex sensitivity (BS). The BS after evoked graded rises in arterial pressure was inhibited significantly whereas that tested after an evoked fall in arterial pressure was augmented significantly in chronic ethanol rats. These changes in BS were not secondary to changes in blood pressure as resting arterial pressure was similar in both groups. However, the heart rate was slightly, but significantly lower in the ethanol group. Challenging isocaloric control and chronic ethanol rats with an acute dose of 0.5 g/kg of ethanol produced nonsignificant changes in BS when evoked changes in blood pressure were both pressor and depressor. A dose of 3 g/kg of ethanol decreased the BS tested after phenylephrine-evoked rises in pressure in both groups; however, the percentage of inhibition of BS was greater in the isocaloric control group. The pressor responsiveness to phenylephrine was reduced slightly in chronic ethanol-treated rats, in contrast to that evoked by angiotensin II which was augmented slightly as compared to the control group. There was no significant difference in the depressor responsiveness to nitroprusside. After injection of acute doses of 0.5 and 3 g/kg of ethanol, the dose-response curves to phenylephrine were shifted to the right in a dose-related fashion in both groups, whereas the angiotensin II and nitroprusside dose-response curve remained unchanged after 0.5 g/kg of ethanol in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed1984

Regulation of estrogen-induced uterine hyperemia and contractility in the guinea pig: cholinergic modulation of an alpha-adrenergic response.

The effects of estradiol (1 microgram: E-1) treatment on uterine hyperemia and uterine sensitivity to various biogenic compounds were evaluated in ovariectomized (OVX) animals treated with either sesame oil or E-1 for 3 days. The E-1 treatments induced significant elevations in uterine weight, blood flow, and alpha- and beta-receptor numbers as compared with oil-treated controls. In contrast, uterine norepinephrine (NE) levels were reduced in E-1-treated, OVX guinea pigs as compared with oil-treated controls. Uterine sensitivity and responsivity to NE (10(-6) M) and acetylcholine (ACH: 10(-8) M) were either comparable to, or enhanced, in E-1-treated animals as compared with controls. In particular, combined ACH-NE treatment induced a dramatic increase in contraction force in E-1-treated uteri as compared with uteri from oil-treated animals. The use of specific adrenergic alpha- (phentolamine: 10(-6) M) or beta- (propranolol: 10(-6) M) receptor blocking agents indicated that the estrogenic response was mediated via the alpha-adrenergic receptor complex. Since atropine (10(-8) M) effectively blocked the cholinergic accentuation of this uterine response, it is suggested that a cholinergic priming, or beta-receptor block, is necessary for the full expression of the alpha-adrenergic-mediated, estrogenic response in the guinea pig. The estrogen-associated increase in available alpha- and beta-receptors and depressed tissue NE levels probably account for both the hyperemic response and enhanced tissue sensitivity to biogenic compounds in the guinea pig.

Acetylcholine↗
PubMed1983

Possible role of adenosine in the CNS effects of ethanol.

The ability of adenosine to modify the CNS effects of acute and chronic ethanol was studied by using theophylline, an adenosine antagonist, and dipyridamole, a blocker of adenosine reuptake. We also studied the binding characteristics of adenosine using crude membranes of whole brain. Theophylline pretreatment prior to acute ethanol administration markedly reduced the duration of ethanol-induced sleep and similarly decreased the intensity and duration of motor incoordination. In chronic ethanol treated mice the effect of theophylline on ethanol-induced hypnosis and motor incoordination was similar to the acute experiment. Dipyridamole markedly prolonged the duration of ethanol-induced hypnosis and potentiated the motor incoordination produced by acute ethanol. However, in chronic ethanol treated mice dipyridamole was not able to potentiate the motor incoordinating effect of ethanol although it was able to prolong ethanol hypnosis similar to the results obtained in the acute ethanol study. Neither drug had any effect on ethanol-induced hypothermia, in either the acute or chronic studies. After 10 days of ethanol ingestion the adenosine dissociation constant was unchanged whereas the number of brain adenosine receptors was increased 28% although the increase did not reach statistical significance. The number of adenosine receptors was reduced 40% at 24 and 48 h after withdrawal and returned to prewithdrawal levels at 72 h. The dissociation constant was reduced at 24 and 48 h but by 72 h had returned to prewithdrawal levels. The marked changes in adenosine binding characteristics as well as the modification of some CNS effects of ethanol by drugs which influence either adenosine binding to its receptor or the availability of adenosine suggests that adenosine may be involved in the expression of some of the CNS effects of ethanol.

Adenosine↗
PubMed1980

Ophthalmomyiasis caused by the sheep nasal bot, Oestrus ovis (Oestridae) larvae, in the Benghazi area of Eastern Libya.

In a two-year study, from January 1977 to December 1978, 80 human cases of ophthalmomyiasis were recorded at the Benghazi Central Eye Clinic. Infections were due to larvae of the sheep nasal bot, Ostrus ovis. The annual incidence was estimated to be 10 per 100,000 population, with most of the cases occurring amongst males during the months of May, June and July. A typical case history is described to illustrate the clinical features and the treatment used.

Adolescent↗
PubMed1979

The anticonvulsant and CNS activity of N-butyryl-N-butylurea in mice.

As a further extension of our studies related to CNS activity of substituted butylureas, a number of derivatives of butylurea were synthesized. Among these a derivative of n-butylurea, N-butyryl-N-butylurea (NBNB) was prepared by acylation of n-butylurea with butyryl chloride in pyridine. The compound was found to possess considerable sedative-hypnotic action. Sleeping time of pentobarbital and barbital was significantly potentiated by NBNB. The compound also exhibited moderate anti-tremorine action and produced significant reduction in the activity ratio for Treadmill experiments. Significant anticonvulsive activity of NBNB was observed against strychnine, pentetrazole and supramaximal electroshock-induced convulsions. In addition to protection against tonic convulsions, the animals were also protected against strychnine and pentetrazole lethality.

Animals↗
PubMed1978

Hypotensive agent from Cynomorium coccineum.

The Iranian plant Cynomorium coccineum was investigated and found to possess significant blood pressure lowering activity in the dog. Extensive chemical isolation and fractionation has revealed that the depressor components were mainly present in the fresh juice of the plant. The fractions, by various organic solvents, of the dried powdered plant lacked significant depressor activity. However, the fresh juice of the plant as well as the water soluble fractions of the fresh juice exhibited strong depressor activity. Spectroscopic metal analysis and infrared and Mass spectra of the active fractions seem to suggest the inorganic nature of these fractions with very low carbon and hydrogen contents which are present, perhaphs, in some special molecular arrangement that becomes disrupted due to sensitivity to the analytical procedures employed.

Animals↗
PubMed1976

Pharmacology of Quercus infectoria.

The galls of Quercus infectoria (Fagaceae), a commonly available plant in Iran, were studied pharmacologically. Two fractions were employed, a dried acetone-treated methanol extract dissolved in water (Fraction A) and a subfraction prepared by chloroform-methanol extraction (Fraction B). Fraction A was active as an analgesic in rats and significantly reduced blood sugar levels in rabbits. Fraction B had CNS depressant activity. Data obtained with a treadmill indicated a decreased activity ratio by Fraction B, suggesting a possible interference in motor coordination. It potentiated the barbiturate sleeping time significantly without changing the onset time or the loss of the righting reflex. In addition, Fraction B exhibited a moderate antitremorine activity by causing a delay in the onset and a decrease in the severity of tremorine-induced tremors. The local anesthetic action of Fraction B was evident due to the complete blockade of the isolated frog sciatic nerve conduction.

Analgesics↗
PubMed1976

Studies on the neuropharmacology of tert-butylurea in mice.

Tertiary butylurea has been investigated neuropharmacologically in mice and rats, and the results indicate that the compound possesses a marked CNS activity. It exhibited a pronounced activity against pentetrazole-induced convulsions and lethality, but the protection against strychnine-induced convulsions and lethality, was only partial. A significant prolongation of pentobarbital sleeping time by a subsedative dose of tert-butylurea was also observed. Protection afforded by tert-butylurea against tremorine-induced tremors and the intensity of its analgesic activity were both of moderate degree. In a subsedative dose range, tert-butylurea exhibited motor incoordination and behavioral effects with a decrease in the minor and the major movements of animals, as apparent from the treadmill and activity meter experiments respectively. The compound, however, does not seem to be a potent sedative-hypnotic agent, although there is a fairly good margin of safety between the hypnotic and the lethal dose orally. The anti-pentetrazole activity of tert-butylurea suggests its possible effectiveness against 'petit mal' seizures and, therefore, calls for additional studies to evaluate the anticonvulsant activity of tert-butylurea.

Analgesics↗
PubMed1975

Biochemorphology of cyclobutanecarbonylureas.

Ten urea derivatives of cyclobutanecarboxylic acid were synthesized and examined for general CNS depressant properties, barbiturate potentiation, and myorelaxant, antitremorine, and anticonvulsant potencies. Although water solubility plays an important role in the activity of these compounds, other factors also appear to be involved. 1-Cyclobutanecarbonyl-3,3-dimethylurea appears to be the most active CNS depressant, whereas 1-cyclobutanecarbonyl-3-(alpha-naphthyl)thiourea is the most active barbiturate potentiator. 1-Cyclobutanecarbonyl-3,3-dimethylurea, 1-cyclobutanecarbonyl-3-phenylurea, and 1-cyclobutanecarbonyl-3-tert-butylurea, 1-cyclobutanecarbonyl-3-allylurea, and 1-cyclobutanecarbonyl-3-phenylurea apparently are the most active against pentylenetetrazol-induced convulsions. 1-Cyclobutanecarbonyl-3-tert-butylurea, 1-cyclobutanecarbonyl-3,3-dimethylurea, and 1-cyclobutanecarbonyl-3-phenylurea are also slightly active tremorine antagonists.

Animals↗
PubMedDate not supplied

Striatal and hypothalamic neurotransmitter changes during ethanol withdrawal in mice.

The alterations in striatal and hypothalamic GABA, DA and its metabolites DOPAC and HVA, and in hypothalamic NE were investigated immediately after ethanol removal and during the withdrawal phase following 10 or 30 days of chronic ethanol administration. After 10 days of ethanol, GABA levels were increased immediately after ethanol removal in both the corpus striatum and the hypothalamus. The concentration of striatal DA was increased at days 2 and 3 of withdrawal and was unchanged at any other time. There was no change in the concentration of DOPAC and HVA in the hypothalamus at any time during withdrawal. Striatal DOPAC and HVA levels were increased only at day 7 of withdrawal after 10 and 30 days of ethanol feeding which was associated with a return of striatal DA to control levels. The concentration of NE in the hypothalamus was increased at days 1, 2 and 7 of withdrawal. After 30 days of ethanol, striatal GABA was increased only at day 7 of withdrawal whereas striatal DA levels were only increased at days 2 and 3 of withdrawal. Hypothalamic NE was markedly increased at days 2, 3 and 7 of withdrawal. The increase in DA concentration associated with no change in DOPA accumulation following inhibition of DOPA decarboxylase and a decrease in the striatal disappearance of DA after alphamethylparatyrosine (alpha-MT) suggests the presence of a hypodopaminergic state. On the other hand an increase in the disappearance of NE in the hypothalamus after alpha-MT suggests an increased NE turnover and a hyperadrenergic state during withdrawal. The increase in striatal GABA at day 7 of withdrawal after 30 days of ethanol may be a rebound phenomenon and may reflect the presence of a hypogabaergic state which has been shown to occur during ethanol withdrawal.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Brain adenosine modulation of behavioral interactions between ethanol and carbamazepine in mice.

The effect of the anticonvulsive drug carbamazepine on ethanol-induced motor incoordination and loss-of-righting reflex was investigated in male CD-1 mice. The results of the investigation showed that carbamazepine significantly potentiated the motor incoordinating effect of ethanol in a dose-dependent fashion. Although carbamazepine did not alter the onset time, it significantly prolonged the duration of ethanol-induced loss-of-righting reflex. Pretreatment with theophylline significantly attenuated the carbamazepine-induced potentiation of ethanol-induced motor incoordination and loss-of-righting reflex. Results from a blood ethanol study indicated no effect of carbamazepine on the clearance of ethanol. The data suggest the involvement of nonadenosinergic mechanism in carbamazepine-ethanol behavioral interactions which is responsible for the accentuating effects of carbamazepine on ethanol-induced motor incoordination and duration of loss-of-righting reflex.

Adenosine↗
PubMedDate not supplied

Cannabinoid-induced motor incoordination through the cerebellar CB(1) receptor in mice.

Cannabinoids are known to impair motor function in humans and laboratory animals. We have observed dose-dependent motor incoordination in mice evaluated by rotorod following direct intracerebellar (i.c.b.) microinjection of synthetic cannabinoid agonists CP55,940 (5-25 microg) and HU-210 (1.56-6.25 microg), through permanently implanted stainless steel guide cannulas. The motor incoordination was marked at 15, 35 and 55 min post-microinjection. The motor incoordination elicited by HU-210 (6.25 microg) and CP55,940 (20 microg) was significantly blocked by the CB(1) receptor-selective antagonist SR141716A (25 microg i.c.b.), indicating mediation by a cerebellar CB(1) receptor. Further direct evidence of CB(1) mediation was obtained through a CB(1) receptor antisense/mismatch oligodeoxynucleotide approach (3 microg/12 h; total of six doses). Mice treated with intracerebellar antisense had a significantly diminished motor incoordination response to intracerebellar CP55,940 15 microg compared to mice that received intracerebellar mismatch or no prior treatment. Also, the response to intracerebellar CP55,940 in the CB(1) mismatch-treated mice did not differ from the mice that received only CP55,940. A separate study using a cerebellar tissue punching technique, following intracerebellar [3H]-CP55,940 microinjection, confirmed that cannabinoid drug dispersion following microinjections was exclusively confined to the cerebellum. Microinjection of CP55,940 (20 microg) into the hippocampus, an area with a large density of CB(1) receptors, did not impair motor coordination. Taken together, these results indicate that cannabinoid-induced motor impairment occurs by activation of a CB(1) receptor in the cerebellum. The participation of other brain motor areas in cannabinoid-induced motor incoordination will require future study.

Animals↗
PubMedDate not supplied

In vivo mammalian metabolism of methylamine and methylurea and their metabolic interrelationship.

The metabolism of methylamine has been investigated in the rabbit and rat, and evidence has been presented to show that the metabolism of the compound leads to the formation and excretion of methylurea, a metabolite suspected, but never conclusively shown, to exist by previous investigators. Urinary methylurea, after the administration of methyl-14C-amine, was shown to have 14C activity at both the carbonyl and methyl portions (groups) of the molecule. 14C activity in the carbonyl group of methylurea was derived from the same metabolic CO2 pool that is used in the formation of urinary urea and respiratory carbon dioxide. Administration of methyl-14C-amine led to the formation of respiratory 14CO2, as noted by various investigators, and it was shown that during a 24-hr period the ratio of specific activity (urea/respiratory CO2) approached 1, in agreement with previous data reported by Mackenzie and du Vigneaud [J. Biol. Chem. 172, 353-354 (1948)]. In order to quantitatively investigate some aspects of metabolism of methylurea, a procedure was developed for the convenient synthesis of N-methyl-14C-carbonyl-urea. In a series of experiments, the urinary urea of the animals injected with N-methyl-14C-carbonyl-urea and N-methyl-14C-urea was examined for radioactivity. Only limited amounts of 14C activity were found in the carbonyl group of urea following administration of N-methyl-14C-urea. However, after the administration of N-methyl-14C-carbonyl-urea, urinary urea contained a 200-fold excess of 14C activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗