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Biomedical subjects

M C Gerald

Publications and source records attributed to M C Gerald.

At least 19 recordsLinked to original sources
PubMed1991

National drug policy and rational drug use: a model curriculum for developing countries.

Of the world's five billion people, 75% of whom live in developing countries, 25-50% have little or no access to basic pharmaceuticals. To ensure an adequate supply of safe and effective drugs of good quality, a national drug policy (NDP) should be incorporated into the national health policy. Elements of a NDP include: identification of therapeutic needs; objective selection of essential drugs; drug supply and distribution system; effective legislation and regulation; quality assurance; manpower development; and dissemination of drug-related information. Drug availability does not ensure their rational prescribing or dispensing or appropriate patient use. It is proposed that a flexible multi-disciplinary curriculum be established for healthcare professionals and students and public policy formulators to provide instruction in NDP elements and the principles of rational drug use. Such courses may stimulate multi-disciplinary drug-related scholarly activities.

Developing Countries↗
PubMed1979

Tolerance to amphetamine-induced impairment of rotarod performance in rats.

Acute administration of d-amphetamine sulfate (30 mg/kg, i.p.) caused muscle weakness and 80% failure in rotarod performance in rats. The incidence of performance failure progressively decreased to 30% in animals receiving d-amphetamine and tested daily for 8 days. A similar progressive reduction in performance impairment was observed in animals receiving d-amphetamine for 3, 5, or 7 days (12.5%) and evaluated only once after the last dose. The tolerance is attributable to a physiological or biochemical rather than learning phenomenon.

Animals↗
PubMed1978

Brain and plasma concentrations of amphetamine isomers in mice.

Brain and plasma concentrations of (+)- and (-)-amphetamine were compared as a function of dose and time after administration to mice. Doses of an amphetamine isomer contained 12 muCi of [14C]-(+) or (-)-amphetamine. Thirty minutes after administration of 2.5, 5 or 10 mg/kg i.p., (+)-amphetamine/(-)-amphetamine concentration ratios in the brain were significantly greater than 1; this ratio was less than 1 for the 15 mg/kg dose. Plasma concentration ratios were significantly greater than 1 for all doses. The ratios of +/-isomers were consistently greater than 1 in brain and plasma when determined at various times (7.5--120 min) after 2.5 and 10 mg/kg i.p. By contrast, i.v. administration of these doses resulted in no isomeric differences in brain amphetamine, alhough plasma (+)-amphetamine/(-)-amphetamine ratios remained somewhat elevated. After SKF 525-A pretreatment, the i.p. and i.v. routes resulted in similar (+)-amphetamince/(-)-amphetamine concentration ratios. These results suggest that (-)-amphetamine has a higher apparent volume of distribution (Vd) than (+)-amphetamine [Vd for (+)- and (-)-amphetamine, 2.5 mg/kg i.v. = 3.35 and 4.61 liters/kg, respectively; Vd for (+)- and (-)-amphetamine 10 mg/kg i.v. = 2.36 and 4.61 liters/kg, respectively] and that the (-)-isomer may be extracted more efficiently by the liver [plasma clearance (V) for (+)- and (-)-amphetamine 2.5 mg/kg i.v. = 6.91 and 9.09 liters/hr/kg respectively; V for (+)- and (-)-amphetamine 10 mg/kg i.v. = 2.85 and 4.33 liters/hr/kg, respectively] resulting in lower plasma and brain concentrations after i.p. administration.

Amphetamine↗
PubMed1977

The effects of amphetamine isomers on rotarod performance.

The amphetamine isomers impair the rotarod performance of rats in a dose-related manner, with (+)-amphetamine approximately four-times as potent as its (-)-isomer. At a rotation speed of 4 rpm, 60 min after i.p. administration, the TD50 values (mg/kg) were: (+)-amphetamine, 24 (21.9-26.4) and (-)-amphetamine, 96 (76.3-118.4), with the curves not deviating from parallelism. Coadministration of the peripheral cholinesterase inhibitor neostigmine salicylate (0.005 mg/kg) attenuated (+)-amphetamine neurotoxicity [30 (26.4-34.1)]. These results, in conjunction with previously reported effects of the drug on isolated nerve-muscle preparations, suggest that the muscle weakness produced by high doses of amphetamine may result from inhibition of transmission at the neuromuscular junction.

Amphetamines↗
PubMed1977

The effects of chronic administration and withdrawal of (+)-amphetamine on seizure threshold and endogenous catecholamine concentrations and their rates of biosynthesis in mice.

The i.v. pentylenetetrazol seizure threshold was increased by 2.5 mg/kg and decreased by 15 mg/kg of a single (+)-amphetamine dose. After 7 consecutive days of amphetamine administration, tolerance developed to the decrease but not to the increase in seizure threshold. At 12--48 h after the last dose of 2.5 mg/kg seizure threshold was decreased, and at 36--48 h after the last dose of 15 mg/kg seizure threshold was increased. After acute and chronic administration of (+)-amphetamine (2.5 mg/kg) endogenous concentrations of whole brain dopamine (DA) were increased and returned to normal levels during the withdrawal period (12--48 h); endogenous norepinephrine (NE) levels were unchanged by acute and chronic drug treatment and during withdrawal. The rates of DA and NE synthesis were increased by chronic amphetamine administration at 24--48 h after drug withdrawal. An acute dose of (+)-amphetamine (15 mg/kg) decreased endogenous levels of DA and NE; normal levels of DA were detected with chronic drug treatment and during withdrawal, with NE remaining slightly depressed. The rates of synthesis of DA and NE were increased by acute and chronic amphetamine treatment and returned to normal 24--48 h after withdrawal. The rebound reversal in seizure threshold after (+)-amphetamine withdrawal suggests an abstinence syndrome that may be interpreted as evidence for the development of physical dependence to (+)-amphetamine after chronic drug administration.

Animals↗
PubMed1977

Catecholaminergic involvement in the effects of amphetamine isomers on seizure susceptibility.

The (+)-amphetamine (2.5 mg/kg) increase in pentylenetetrazol seizure was abolished by pretreatment with reserpine, alpha-methyltyrosine methyl ester (alpha-MT), FLA-63 or 6-hydroxydopa. All treatments except reserpine antagonized the increase in seizure threshold produced by (-)-amphetamine (4 mg/kg). Only reserpine +alpha-MT antagonized the decrease in seizure threshold produced by (+)-amphetamine (15 mg/kg). These results indicate that amphetamine alterations in PTZ seizure susceptibility are mediated indirectly via the release of newly synthetized and/or granular stores of catecholamines.

Amphetamine↗
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↗