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Biomedical subjects

F R Domer

Publications and source records attributed to F R Domer.

At least 37 records · Page 2Linked to original sources
PubMed1980

Effects of lead on movement of albumin into brain.

The offspring of CD-1 mice were exposed either to 0.5% sodium acetate or lead acetate in the drinking water from the time of birth. After weaning, locomotor activity was evaluated. The lead-exposed mice were hyperactive and smaller than the sodium-exposed mice. Methylphenidate, caffeine, ephedrine and pemoline all caused an increase in the movement of radioiodinated serum albumin (RISA) into the brain of sodium-exposed mice. In the lead-exposed animals the movement of RISA into the brain was decreased in the mice given saline (control), amphetamine, methylphenidate or ephedrine relative to the corresponding sodium-exposed animals. These changes are opposite to those previously found using radioactive pertechnetate as the probe of the function of the blood-brain barrier (BBB). This provides further evidence for the selectivity of the BBB in handling different types of molecules.

Albumins↗
PubMed1978

Involvement of the sympathetic nervous system in the urinary bladder internal sphincter and in penile erection in the anesthetized cat.

Male cats were anesthetized with pentobarbital. In one series of experiments a Foley catheter was placed suprapubically in the urinary bladder and physiologic saline, under a constant head of pressure, was allowed to flow at a constant rate through the bladder. Alpha-adrenergic stimulants such as ephedrine, norepinephrine, or methoxamine all caused a decrease or cessation in urinary flow. This effect was reversed by the alpha-adrenergic blocking agent, phentolamine. In addition, phentolamine administration caused penile erection. Erection also occurred after administration of the alpha-adrenergic blocking agent, phenoxybenzamine, or the beta2-adrenergic stimulants terbutaline or salbutamol. In each case the erection could be reversed, and usually terminated completely, by administration of the beta-adrenergic blocking agent, propranolol. Hypotension per se was not the required event to initiate erection because administration of acetylcholine, histamine, or prostaglandin E2 did not result in penile erection. In two of five experiments nitroprusside caused an erection. It was concluded that a predominance of beta2 activity in the penile vasculature is involved in erection.

Animals↗
PubMed1977

Cardiovascular and neuromuscular effects of dimethyl sulfoxide in anesthetized rabbits.

In rabbits anesthetized with pentobarbital, the carotid arterial blood pressure and bilateral contractions of the gastrocnemius muscles due to electrical stimulation of the sciatic nerves were recorded. Intravenous administration of up to 1 ml of dimethyl sulfoxide/kg caused profound hypotension and eventually failure of neuromuscular transmission. Caution must be used in considering dimethyl sulfoxide as a solvent for drug administration.

Animals↗
PubMed1977

Effect of sulfur substitution for the noncarbonyl oxygen in hemicholinium-3 and acetyl-seco-hemicholinium-3. Synthesis, biological activity, and structure-toxicity relationships.

As a continuation of our efforts to develop and study inhibitors which act presynaptically on neuromuscular function, sulfur analogues of hemicholinium-3 (HC-3, 1) and acetyl-seco-hemicholinium-3 (AcHC-3, 3) were prepared. In each case sulfur is substituted for the noncarbonyl oxygen in HC-3 (1) and AcHC-3 (3). As expected on the basis of conformational differences between acetylcholine and acetylthiocholine both of the thio analogues are produced in the seco form and do not cyclize spontaneously or when subjected to aqueous, acidic conditions up to 100 degrees C. Both compounds are stable in aqueous pH 7.4 solutions at 37 degrees C and in slightly acidic D2O solutions for more than 24 h. While thio-seco-hemicholinium 3 (11) is stable in the presence of acetylcholinesterase and butyrylcholinesterase in H2O at pH 7.4, acetylthio-seco-hemicholinium-3 (12) reacts within seconds to form the hemiacetal form of thiohemicholinium-3 (16). Mouse toxicity studies (LD50) indicate that while 12 is approximately as toxic as HC-3 (1) and AcHC-3 (3), 11 is 226 times less toxic. As in the studies with 1 and 3, mice were protected from 11 by choline and slightly by neostigmine. It is of interest, however, that almost equal and intermediate protection against 12 was afforded by choline and neostigmine. Structure-toxicity relationships of 1,3,11, 12, and 16 are discussed.

Acetylation↗
PubMed1977

Biological evaluation of some biphenyl analogs of acetyl-seco-hemicholinium No. 3.

The oxygen atoms in the esteratic moiety of acetyl-seco-hemicholinium No. 3 (AcHC-3) were replaced with carbon to form the ether, ketone and aliphatic analogs. Also, the thio and acetylthio-seco analogs of hemicholinium No. 3 (HC-3) were studied. When evaluated in the rabbit sciatic nerve-gastrocnemius muscular preparation all of the analogs caused neuromuscular blockades in two or three separate phases. The first phase of blockade caused by the ketone and thio analogs was rapid in onset and reversed by neostigmine. It was presumably competitive in type. The first phase of blockade caused by the ether and aliphatic analogs was increased by neostigmine and was concluded to be of the non-competitive type. All analogs caused a second phase of blockade that was reversed by choline and is typical of HC-3. A third blockade was found following the ether and ketone analogs. All of the analogs were more active as inhibitors of the true and pseudocholinesterases than was HC-3. All of the analogs were much less potent as inhibitors of acetylcholine synthesis than was AcHC-3. The implications of these findings are discussed.

Acetylcholine↗
PubMed1977

Effects of probenecid on methotrexate exchange between the blood and the cerebrospinal fluid.

In rabbits anesthetized with urethane, only a small fraction of 3H-methotrexate administered by an i.v. infusion reached an artificial cerebrospinal fluid solution perfused through the cerebroventricular system. This movement was not altered significantly by probenecid administered either i.v. or in the perfusing artificial cerebrospinal fluid. When the 3H-methotrexate was perfused through the cerebroventricular system, one third of the amount normally lost during the perfusion was retained when probenecid was also added to the solution. Therefore, at least a portion of the apparent blood-brain barrier that exists for methotrexate is due to removal from the cerebrospinal fluid by a process that can be inhibited by probenecid.

Animals↗
PubMed1976

Synthesis and structure-toxicity relationships of three new stable analogues of acetyl-seco-hemicholinium-3.

In order to develop and study inhibitors of neuromuscular function which act presynaptically, three stable analogues of acetyl-seco-hemicholinum-3 (AcHC-3,2) were prepared. These analogues have 2-ethoxyethyltrimethylammonium, 4-oxopentyltrimethylammonium, and n-pentyltrimethylammonium moieties substituted for the 2-acetylethyltrimethylammonium (acetylcholine) moieties of AcHC-3 (2) to form the ether 2, ketone 4, and alkane 5 analoggues of AcHC-3 (2). Although AcHC-3 (2) has been shown to undergo deesterification rapidly in basic solutions and slowly at pH 7.4, it has been found to be stable in H2O or D2O under slightly acidic conditions. All of the analogues are stable for extended time under both slightly acidic conditions and at pH 7.4 in H2O or D3O. It has been found that 2 reacts with acetylcholinesterase and butyrylcholinesterase within seconds in H2O at pH7.4. However, deesterification of 2 with subsequent cyclization to the hemiacetal form of hemicholinium-3 (HC-3, 1) is prevented at pH 7.4, possibly by an irreversible binding of 2 to the enzyme. The analogues 3-5, however, do not react under identical conditions. Mouse toxicity studies (LD50) indicate that 2 is approximately as toxic as HC-3 (1), whereas 3, 4, and 5 are 14.2, 23.8, and 43.1 times less toxic, respectively. The toxic effects of 3-5, like 1 and 2, are antagonized by choline but not by neostigmine in mice. Structure-activity relationships of 2-5 are discussed.

Animals↗