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Biomedical subjects

D N Johnson

Publications and source records attributed to D N Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1989

Benzo- and pyrido-1,4-oxazepin-5-ones and -thiones: synthesis and structure-activity relationships of a new series of H1 antihistamines.

A series of novel benzo- and pyrido-1,4-oxazepinones and -thiones which represents a new structural class of compounds possessing H1 antihistaminic activity was synthesized, and the SARs were evaluated. The antihistaminic activity was determined by blockade of histamine-induced lethality in guinea pigs. The sedative potential was determined by comparison of the EEG profiles of the compounds with those of known sedating and nonsedating antihistamines. Several of the compounds were shown to possess potent H1 antihistaminic activity and to be free of the cortical slowing with synchronized waves and spindling activity found in the EEG of sedative antihistamines. One compound, 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4- oxazepine-5(2H)-thione (rocastine) is currently undergoing clinical evaluation as a nonsedating H1 antihistamine.

Animals↗
PubMed1986

Antagonism of cisplatin-induced emesis by metoclopramide and dazopride through enhancement of gastric motility.

The antiemetic activity, gastric motor activity, and dopamine receptor effects of metoclopramide, dazopride, and sulpiride were assessed to establish if enhancement of gastric motility or antagonism of central dopamine receptors is the predominant action for drug-induced suppression of cisplatin-induced emesis. Emesis produced in dogs by cisplatin is antagonized by metoclopramide and dazopride. The antiemetic actions of metoclopramide and dazopride are associated with their ability to enhance gastric motor activity. Dazopride, unlike metoclopramide, has minimal dopamine receptor antagonist properties. Sulpiride is a potent dopamine receptor antagonist; however, it had no effect on the stomach and was ineffective in suppressing cisplatin-induced emesis.

Animals↗
PubMed1983

Aminoalkylindoles: atypical dopamine antagonists.

The neuropharmacological profile of a series of aminoalkylindole compounds (AHR 1229-(3-[2-(3-indolyl)-ethyl]-butylamino-1-phenyl-pyrrolidine), AHR1771-(1-[2-(2-methyl-3-indolyl)ethyl]-4-phenyl-3,4-dehydropiperidine), AHR1806-(1-[2-(5-chloro-3-indolyl)-ethyl]-4-phenyl-3,4-dehydropiperidine), AHR1858-(1-[2-(3-indolyl)ethyl]-4-(4-fluorophenyl)-1,2,3, 6-tetrahydropyridine), AHR1709-(1-[2-(3-indolyl)ethyl]-4-phenyl-1,2,3,6-tetrahydropyridine) was determined in comparison with the classical neuroleptic agents haloperidol and oxypertine, the latter being of similar indole structure. The indole analogues were shown to antagonize amphetamine-induced toxicity in aggregated mice, to indicate a 'tranquillizing' action but, in contrast to haloperidol and oxypertine, showed weak or no activity in other classical behavioural tests for neuroleptic action, catalepsy induction and stereotypy antagonism. In further contrast to haloperidol or oxypertine, the indole derivatives failed to displace [3H]spiperone in radioligand binding assays and failed to increase prolactin levels. However, similarly to both typical and atypical neuroleptic agents, the indole derivatives were shown to inhibit the behavioural hyperactivity resulting from the intracerebral administration of dopamine into the mesolimbic nucleus accumbens of rat. The dissociation of an ability to antagonize a dopamine action in the mesolimbic system from classical neuroleptic actions involving other cerebral dopamine systems is the most important finding of the present study.

Amphetamine↗
PubMed1980

PGD2 effects on rodent behavior and EEG patterns in cats.

Prostaglandin (PG) D2 was studied to determine the pharmacological effects of this PG on the central nervous system. PGD2 (0.45-4.05 mg/kg) decreased spontaneous locomotor activity in rats by as much as 66% of control, however, the neuromuscular coordination of mice, treated at the same doses of PGD2, was not impaired. PGD2 (0.05-4.05 mg/kg) also increased pentobarbital sleeping time in mice from 42% to 238% of control, in a dose-related manner. PGD2 did not prevent convulsions induced in response to electroshock or pentylenetetrazol. Cats monitored for EEG responses to PGD2 infusion displayed variable sensitivity to different doses (16-3000 microgram) of drug, however, the characteristic response to PGD2 was the conversion from a uniform low voltage, fast wave pattern to high voltage, slow waves. Cats administered PGD2 were sedated and sometimes catatonic, and displayed brief periods of hypotension, bradycardia, diarrhea, analgesia and hyperthermia at higher doses of the drug. Thus, PGD2 possesses sedative properties in rodents and cats and may have a role in the central nervous system.

Animals↗
PubMed1979

AHR-6646: a new, long-acting neuroleptic.

1. AHR-6646 blocked d-amphetamine lethality in mice under aggregated conditions when the pretreatment interval was between one hour and seven days. 2. Conditioned avoidance responding in mice and cats was suppressed by AHR-6646 in doses that did not impair escape behavior. The duration of this effect was markedly prolonged. 3. AHR-6646 produced catalepsy in rats. The onset of this effect was delayed and the duration was prolonged when compared with that of chlorpromazine. 4. Apomorphine-induced pivoting in mice with unilateral lesions of the caudate nucleus was suppressed by AHR-6646. 5. AHR-6646 was a potent antiemetic agent in dogs, with a delayed onset and prolonged duration of action.

Animals↗
PubMed1978

Effect of diazepam on food consumption in rats.

Diazepam significantly increased milk consumption in rats that had never been exposed to this food before but not in rats trained to drink milk. Diazepam failed to increase lever-pressing for food reward except when this behavior had been previously suppressed by the simultaneous administration of electric shock. These data suggest that diazepam does not alter appetite, but enhances the expression of motivation suppressed by instinct or training.

Animals↗
PubMed1978

(1-(3-(Phenothiazin-10-yl)propyl)-4-piperidinyl)phenylmethanones, a novel class of long-acting neuroleptic agents.

In previous studies the phenyl-4-piperidinylmethanone moiety was shown to be a neuroleptic pharmacophore. A short series of [1-[3-(phenothiazin-10-yl)propyl]-4-piperidinyl]phenylmethanones was prepared and tested for neuroleptic activity using the blockade of d-amphetamine lethality in aggregated mice and suppression of conditioned avoidance behavior as the end points. Most compounds were shown to be potent neuroleptic agents and two were found to possess a long duration of action.

Animals↗