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Biomedical subjects

J Offermeier

Publications and source records attributed to J Offermeier.

At least 19 recordsLinked to original sources
PubMed1987

Apparent central neurotransmitter receptor changes induced by low-level lead exposure during different developmental phases in the rat.

Three groups of male Wistar rats were exposed to low concentrations of lead during different phases of their development for periods of 21 days. Exposure was initiated at conception (group I), at parturition (group II), or after weaning had occurred (group III). Mean brain lead levels achieved immediately after exposure were 1.07 +/- 0.15, 0.84 +/- 0.06, and 0.44 +/- 0.06 microgram/g in groups I, II, and III, respectively. On Day 64 postpartum radioligand binding studies were performed to determine apparent receptor densities (Bmax values) and affinities (KD values) in brain membranes of the lead-exposed rats. Lead exposure during the neonatal phase (group II) resulted in significant increases of the apparent densities of forebrain alpha 1-adrenoceptors (by 92%), cortical beta-adrenoceptors (by 116%), and striatal D-2 dopamine receptors (by 133%). Lead exposure also resulted in a significant decrease of the apparent density of striatal muscarinic receptors in group I (by 43%) and group II (by 25%) and an increase in the apparent density of hippocampal S1 receptors in group II (by 78%). Lead exposure after weaning had occurred did not alter the apparent densities of any of the receptors investigated. Receptor affinity changes, which were not identical in the three groups of rats, were also induced by lead exposure. The developmental phase during which exposure occurs appears to be a determinant of the type of neurotransmitter receptor changes induced by lead.

Animals↗
PubMed1986

A comparative study of the locomotor activity effects of apomorphine and the "atypical dopamine agonists" (piribedil and S3608).

Apomorphine and the "atypical dopamine agonists" (piribedil and S3608) dose dependently increase locomotor activity (LA) in rats. The LA effects of all 3 drugs are readily attenuated by pretreatment with pimozide or sulpiride. Reserpine pretreatment or bilateral 6-hydroxydopamine lesions of the nucleus accumbens (NAS) potentiates apomorphine-induced LA but attenuates piribedil- and S3608-induced LA. The latter suggests an indirect mode of action for piribedil and for S3608. However, piribedil and S3608 at concentrations up to 10(-4)M do not cause release or inhibition of 3H-dopamine uptake in synaptosomes prepared from the rat NAS. Sulpiride antagonism of apomorphine-induced LA is surmountable by increasing the dose of apomorphine. Antagonism of piribedil- or S3608-induced LA by sulpiride is not surmountable by increasing the dose of either of the "atypical dopamine agonists". Furthermore, pretreatment with either piribedil or S3608 substantially increases the peak LA inducible by apomorphine. The effects of simultaneous injections of piribedil and S3608 are, however, not additive. These findings suggest that the LA stimulant effects of piribedil and S3608 are mediated via receptors or systems which differ from the receptors involved in the mediation of apomorphine-induced LA.

Animals↗
PubMed1986

The alpha 1- and alpha 2-adrenoceptor selectivity of drugs with potential effects on blood pressure--a radioligand-binding study.

In screening compounds with potential antihypertensive properties, the determination of their relative selectivities for alpha 1- and alpha 2-adrenoceptors is important not only for the elucidation of their mechanisms of action but also, possibly, for the assessment of their potential side-effects. The relative selectivity of a number of drugs for alpha 1- and alpha 2-adrenoceptors was determined by means of radioligand-binding studies. The alpha-adrenoceptor antagonists prazosin and indoramin display selectivities for alpha1-adrenoceptors of about factors 1 000 and 4 000 respectively. The alpha-adrenoceptor agonists clonidine and 2-(3,4-dihydroxyphenylimino)-imidazoline (DPI) display selectivities for alpha 2-adrenoceptors of about factors 200 and 300 respectively. The alpha-adrenoceptor antagonist mianserin displays approximately equal, albeit relatively low, affinities for alpha 1- and alpha 2-adrenoceptors. In view of the distribution of alpha 1- and alpha 2-adrenoceptors in vascular smooth muscle and in the reflex arcs controlling blood pressure, the low incidence of reflex tachycardia associated with the use of prazosin and indoramin can be explained on the basis of their alpha 1-adrenoceptor selectivity. Similarly, the hypertensive crisis which may follow the withdrawal of clonidine can be explained on the basis of a selective alpha 2-adrenoceptor agonistic action. The finding that mianserin has such low affinities for both alpha 1- and alpha 2-adrenoceptors may explain why, at therapeutically effective antidepressant dosages, it is usually devoid of adverse haemodynamic effects.

Adrenergic alpha-Agonists↗
PubMed1985

Pharmacokinetics of the benzodiazepines.

At present several benzodiazepines are available for clinical use. Pharmacological and clinical studies have failed to show qualitative differences between them. The main variations among individual benzodiazepines are in their pharmacokinetics and metabolism. The differences in the rates of absorption, volumes of distribution, distribution half-lives, compartmental kinetics, metabolism and elimination half-lives between individual benzodiazepines are reviewed. These influence the selection of a particular benzodiazepine for a specific patient or condition. Guidelines for particular clinical situations are provided.

Adult↗
PubMed1984

Opioid drugs and their receptors. A summary of the present state of knowledge.

New developments in the field of opioid pharmacology have necessitated the reclassification of drugs formerly lumped together as 'narcotic analgesics'. Various developments pertaining to the characterization of opioid receptors, endogenous 'opioid ligands' and the subclassification of opioid receptors are reviewed. At the moment no entirely satisfactory classification of opioid analgesics appears to be possible; however, these drugs can be divided into 'agonist' and 'agonist-antagonist' analgesics on the basis of their interactions with mu-, kappa- and sigma-receptors. Individual agonist and agonist-antagonist analgesics vary in their analgesic potencies. However, by selecting the correct dosage analgesic effects approximately equivalent to those of 10 mg morphine can be achieved with most of these drugs. The agonist analgesics produce morphine-like 'drug-seeking behaviour' and have a high potential for abuse; the agonist-antagonist analgesics generally have a lower potential for abuse. The agonist-antagonist analgesics are not a homogeneous group; some of these compounds produce psychotomimetic and adverse haemodynamic effects, this probably being due to interaction with sigma-receptors. Nalbuphine, an agonist-antagonist analgesic devoid of 'sigma effects', appears to be an interesting new drug in the development of opioid analgesics with more selective actions.

Analgesics, Opioid↗
PubMed1977

Studies of the pharmacology of a new antidepressant, S1694.

A new antidepressive drug, S1694, produces increased locomotor activity (LA) in mice, but less so than d-amphetamine. This effect is decreased by pimozide, phenoxybenzamine, as well as by pretreatment of the animals with reserpine or alpha-methyl-p-tyrosine methyl ester (H44/68). S1694 inhibits active dopamine (DA) uptake into rat striatal synaptosomes, but not noradrenaline (NA) uptake into rat hypothalamic synaptosomes, or serotonin (5-HT) uptake into rat midbrain synaptosomes, in the concentrations used. The inhibition of DA uptake appears tp be competitive and the inhibition constant estimated is 1,3 X 10(-6) M. In addition, S1694 releases DA in the same concentrations, and NA as well as 5HT at higher concentrations. It is concluded that S1694 activates LA primarily by inhibitionof DA re-uptake and DA release. The central DA system activation may be important in the antidepressive effect.

Animals↗
PubMed1977

South African multicentre study of metoprolol and propranolol in essential hypertension.

Ninety-three patients diagnosed as essential hypertensives, WHO stage I or II, entered this double-blind trial comparing 2 dose levels of CGP 2175-H 93/26 (metoprolol) with 2 doses of propranolol. Treatment on active medication was maintained for 6 weeks and was started after a 2-week washout and a 2-week placebo period. Twelve patients dropped out of the trial for reasons not related to the drugs and 1 patient was regarded as a therapeutic failure. Efficacy was assessed by measuring the diastolic and systolic blood pressure, pulse rate and by noting any significant ECG changes. All treatments reduced and maintained a lower blood pressure. However, a reduction with 360 mg propranolol per day was not statistically significant. Metoprolol 120 mg/d was significantly superior to propranolol 240 mg/d in holding the diastolic supine blood pressure at less than or equal to 90 mmHg. Metoprolol 120 mg/d and 210 mg/d pooled results were significantly superior to the propranolol 240 mg/d and 360 mg/d pooled data in maintaining a diastolic blood pressure of less than or equal to 90 mmHg. All treatments were well tolerated and in no case was it necessary to withdraw owing to adverse effects. No significant difference was detected between the treatments with respect to therapeutic emergent symptoms and signs. Laboratory results remained normal with all treatments.

Clinical Trials as Topic↗
PubMed1977

Sensitization of contracted tracheal smooth muscle to beta-adrenergic spasmolysis by subthreshold doses of papaverine.

In certain cases beta-adrenergic substances cause little or no relaxation of tracheal or bronchiolar smooth muscles contracted by spasmogenic mediators. This phenomenon is explained on the basis of the model of functional antagonism, with the suppositions that the spasmogenic system has a reserve and the spasmogen concentrations are much higher than the concentration which would cause a just-maximal contraction. If this is correct, the model predicts that it should be possible to restore the effectiveness of the beta-adrenergic spasmolytics with low doses of a non-competitive (metactoid) spasmolytic, provided that this substance acts by depressing the subeffect curve. Such a metactoid antagonist should cause the desired result in subthreshold concentrations, i.e. concentrations which as such do not cause relaxation of the contracted muscles. In a series of experiments on the isolated tracheal chain of the guinea-pig the results agreed with this expectation. This provides additional proof for the model of functional interaction and suggests that the combination of beta-adrenergics with low doses of a metactoid spasmolytic may be of clinical interest.

Adrenergic beta-Agonists↗
PubMed1977

An alternative model for non-competitive antagonism.

An antagonist acting on its own receptor leading to a gradual decrease in the affinity between an agonistic drug and its own but different receptor, is a metaffinoid antagonist. The presently published models for metaffinoid antagonism predict a parallel shift in the concentration-effect curves of the agonist by the metaffinoid antagonist, due to a gradual change in the affinity between the agonist and its receptor. An alternative model is proposed where the presence of an antagonist changes the affinity of only a fraction of the agonistic receptors, leading, in contrast to the presently published model to: a) non-parallel shifts in concentration-effect curves and b) metaffinoid antagonistic curves that look like the curves obtained in metactoid antagonism. Experimental support for the alternative model is found in the interaction between various beta-adrenergic agonists and serotonin in the guinea-pig tracheal chain and rat stomach fundus strip preparations.

Animals↗