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Biomedical subjects

M C Gerald

Publications and source records attributed to M C Gerald.

At least 55 records · Page 3Linked to original sources
PubMed1977

3,4-Methylenedioxyphenyl-, isopropylidenedioxyphenyl-, and benzyl-substituted chiral 2-aminosuccinimides and 3-aminopyrrolidines. Stereoselective investigations of potential anti-parkinsonian, antipsychotic, and anticonvulsant activities.

The chiral title compounds 2--11 were assessed for their potential anti-Parkinsonian, antipsychotic, and anticonvulsant properties. The most striking differences in the biological activity of enantiomeric pairs were noted for D-(R)-2-amino-N-(3,4-methylenedioxyphenyl)succinimide hydrochloride (2) vs. L-(S)-3 and D-(R)-2-amino-N-(3,4-isopropylidenedioxyphenyl)succinimide (4) vs. L-(S)-5. D-(R)-2-partially attenuated amphetamine-induced stereotyped behavior, whereas D-(R)-4 antagonized oxotremorine-induced tremors. Their respective enantiomorphs were inactive in these tests. No differences in anticonvulsant potency of enantiomeric pairs were observed. The stereoselective actions of D-(R)-2 and 4 were rationalized on the basis of the presence or absence of gem-dimethyl functions in isopropylidenedioxy vs. methylenedioxy groups; the data seem to indicate that these methyl groups influence selective receptor site interaction in the D-(R) series.

Animals↗
PubMed1976

Studies on the effects of histaminergic agents on seizure susceptibility in mice.

The influence of pharmacological modifications of the functional activity of the central histaminergic system was studied on the susceptibility of mice to pentylenetetrazol-induced minimal (clonic) and maximal (tonic) seizures. Enhancement in the functional activity of the system by central administration of histamine or 4-methylhistamine of peripheral L-histidine loading failed to modify the risk of seizures. By contrast, reduction in histaminergic function was found to alter seizure susceptibility. Brocresine, an inhibitor of histamine synthesis, decreased and increased the risk of pentylenetetrazol-induced minimal and maximal seizures, respectively. Many, but not all, classical anti-histamines (H1 antagonist) and metiamide (H2 antagonist) and metiamide (H2 antagonist) increased minimal seizure susceptibility after periheral and intraventricular administration, respectively.

Animals↗
PubMed1976

8-chloro-(S)- and -(R)-10-((S)-and -(R)-3'-methylethylaminopyrrolidino)- 10,11-dihydrodibenzo(b,f)thiepins. Synthesis and pharmacological studies.

The synthesis for 8-chloro-(S)- and -(R)-10-[(S)- and -(R)-3'-methylethylaminopyrrolidino]-10,11-dihydrodibenzo[b,f]thiepins is presented. The absolute configuration at position 3' of the aminopyrrolidino side chain is known from synthesis and corresponds to the asymmetric carbon atom in (S)- or (R)-aspartic acid. The absolute configuration at C-10 of the dihydrodibenzo[b,f]thiepin ring system was deduced from ORD-CD analysis coupled with degradation of partially resolved (+)-8-chloro-10-amino-10,11-dihydrodibenzo[b,f]thiepin to (+)-(S)-1,2-diphenylethylamine. The four isomers were studied in mice for their ability to block conditioned avoidance responding, antagonize oxotremorine, and act as analgetics and anticonvulsants. These compounds were found to be nonselective antagonists of histamine, acetylcholine, and BaCl2 in vitro. The compounds exerted effects similar to those of chlorpromazine. Stereoselective differences in activity between diastereoisomers, rather than between enantiomorphs, were generally observed.

Analgesics↗
PubMed1976

Para-substituted N-acetyl-L(S)- and -D(R)-alpha-amino-N-phenylglutarimides. A structure-activity study of substituent effects on steroselective anticonvulsant activity.

For purposes of carrying out structure-activity studies on a series of pure R and S enantiomorphs of various para-substituted N-acetyl-alpha-amino-N-phenylglutarimides, we synthesized the p-acetyl, iodo, cyano, ethyl, and n-butyl analogues. These compounds complimented previous R and S isomers (unsubstituted and the p-chloro, methyl, nitro, and methoxyl analogues) synthesized in our laboratories from amino acids of known absolute configuration. The neurotoxic doses (TD50's), anticonvulsant potencies [maximal electroshock seizures (MES) and subcutaneous metrazole (sc Met) ED50's], protective indices (PI = TD50/ED50), and effects on minimal seizure threshold (iv Met) were compared with similar values concomitantly determined for clinically employed anticonvulsants. A parallel relationship was shown between neutotoxicity (TD50) and potency (ED50) for the R and S analogues. In most cases R isomers had a more rapid onset of action and possessed greater neurotoxicity and greater anticonvulsant potency.

Animals↗
PubMed1976

Determination of endogenous concentrations of norepinephrine and dopamine and their rates of synthesis in a single mouse brain: biphasic effects of (+)-amphetamine.

A method is described that possesses sufficient sensitivity to permit the simultaneous fluorometric assay of endogenous concentrations of tyrosine, dopamine and norepinephrine, and the measurement of the estimated rate of synthesis of 3H-dopamine and 3H-norepinephrine from 3H-tyrosine in a single mouse brain. (+)-Amphetamine elicited a biphasic effect reducing the estimated rate of synthesis of dopamine and norepinephrine at 5 mg/kg, while lowering the endogenous concentrations of these catecholamines and increasing their rates of synthesis at 15 mg/kg.

Animals↗
PubMed1975

Amphetamine tachyphylaxis in the pithed guinea-pig.

A single dose of (+)-amphetamine (8 mg kg-1, i.p.) administered 4 h before experimentation, reduced the pressor and positive chronotropic effects elicited by this drug (0-6 mg kg-1, i.v.) and augmented the rate of the development of tachyphylaxis to these responses in the pithed guinea-pig preparation. Amphetamine pretreatment reduced the pressor and positive chronotropic effects of phenylephrine (0-1 mg kg-1, i.v.) and the positive chronotropic effects of angiotensin (30 mug kg-1, i.v.). The rate of the development of tachyphylaxis to the cardiovascular responses elicited by phenylephrine and angiotensin was augmented by amphetamine pretreatment. The results suggest that an indirect mechanism (noradrenaline) may in part mediate the cardiovascular effects of these 3 drugs and/or that amphetamine may act as a competitive antagonist at adrenoceptor sites.

Angiotensin Amide↗
PubMed1975

Effects of methamphetamine on the isolated rat phrenic nerve-diaphragm preparation.

Low concentrations of methamphetamine facilitated twitch, while higher concentrations produced dose-dependent blockade of twitch indirectly elicited. Methamphetamine facilitated twitch elicited by direct stimulation; These findings suggest that methamphetamine-induced enhancement in physical endurance and performance in moderate doses, and muscle weakness at high doses, may be attributed to drug effects at a peripheral site of action.

Animals↗