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Biomedical subjects

M K Menon

Publications and source records attributed to M K Menon.

At least 37 records · Page 2Linked to original sources
PubMed1981

Modification of apomorphine hypothermia by drugs affecting brain 5-hydroxytryptamine function.

Intraperitoneal administration of apomorphine caused hypothermia in mice. Pretreatment with the serotonin (5-HT) receptor antagonists methysergide (3 mg/kg), cinanserin (10 mg/kg) or brom-LSD (3 mg/kg) potentiated this response of apomorphine. Brain 5-HT depletion by p-chlorophenylalanine caused similar modification. On the contrary, the 5-HT receptor agonists quipazine (3 mg/kg) and MK-212 (3 mg/kg), significantly blocked apomorphine hypothermia. It was concluded that 5-HT modulates the dopamine (DA)-mediated body temperature changes and that drug-induced alterations in the brain 5-HT function modify apomorphine-induced hypothermia in a predictable manner. One mg/kg dose of lysergic acid diethylamide (LSD) blocked apomorphine hypothermia. The apomorphine-blocking effect of both quipazine and LSD developed tolerance. Moreover, LSD showed cross tolerance with quipazine. It was concluded that the hypothermia-blocking property of LSD resides on its ability to activate the hypothalamic 5-HT receptors.

Animals↗
PubMed1981

Serotonergic drugs, benzodiazepines and baclofen block muscimol-induced myoclonic jerks in a strain of mice.

In male Swiss mice, muscimol produced myoclonic jerks. A 3 mg/kg (i.p.) dose induced this response in all of the mice tested and the peak response of 73 jerks per min was observed between 27 and 45 min. Increasing the brain serotonin levels by the administration of 5-hydroxytryptophan (80-160 mg/kg) in combination with a peripheral decarboxylase inhibitor resulted in an inhibition of the muscimol effect. However, in a similar experiment l-dopa (80-160 mg/kg) was without effect. In doses of 3-10 mg/kg, the serotonin receptor agonist MK-212 caused a dose-dependent blockade of the response of muscimol. Of the benzodiazepines, clonazepam (0.1-0.3 mg/kg) was found to be several fold more potent than diazepam (0.3-3 mg/kg) in blocking the myoclonic jerks. While (-)-baclofen (1-3 mg/kg) proved to be an effective antagonist of muscimol, its (+)-isomer (5-20 mg/kg) lacked this property. Considering the fact that 5-HTP and the benzodiazepines have been found to be beneficial in the management of clinical myoclonus, the muscimol-induced myoclonus seems to be a satisfactory animal model that may prove useful for the development of new drug treatments for this condition. Our present study indicated the possible value of MK-212 and (-)-baclofen in the management of clinical myoclonus.

5-Hydroxytryptophan↗
PubMed1981

A new method for the evaluation of benzodiazepines based on their ability to block muscimol-induced myoclonic jerks in mice.

A number of clinically used benzodiazepines were tested for their effectiveness in blocking muscimol-induced myoclonic jerks in mice. Their ED50 values were determined from their dose-response curves. These data gave the following relative potencies with respect to diazepam: diazepam = 1, medazepam = 0.24, oxazepam = 1.27, flurazepam = 1.90, lorazepam = 3.01, nitrazepam = 3.93, clonazepam = 33.14, and flunitrazepam = 116.00. Because our earlier studies indicated that muscimol-induced myoclonic jerks probably originate from the spinal cord, the present method may prove to be suitable for quantitatively evaluating the effect of benzodiazepines on the spinal cord. The present results also indicate the possible value of flunitrazepam in the management of neurologic disorders in which preferential action on the spinal cord is desired.

Animals↗
PubMed1980

An electromyographic method for the assessment of naloxone-induced abstinence in morphine-dependent rats.

The electromyographic (EMG) activities of suprahyoideal muscle were recorded to measure naloxone-precipitated abstinence signs in morphine-dependent rats anesthetized with urethane (1 g/kg). Rats were rendered dependent on morphine by implanting 2 morphine pellets (75 mg each) and abstinence signs were induced by intravenous injections of various doses of naloxone at different times after pellet implantation. Three precipitated abstinence signs, a) myoclonic twitch activity (MTA), b) mastication, and c) body shakes were observed on EMG recordings after the injection of naloxone. Of these symptoms, only the MTA induced by naloxone (10 microgram/kg) occurred 4h after pellet implantation and its sensitivity to naloxone increased with prolonged pellet implantation. Both mastication and precipitated shakes could be induced at 24h. However, higher doses of naloxone were required to produce the shakes than is required to induce mastication. There appears to be a positive correlation between the intensity of naloxone-induced MTA and the degree of physical dependence on morphine. Since the MTA and mastication can be induced by low doses of naloxone in morphine-dependent rats, we suggest that these two parameters may be used to detect morphine abstinence signs in this species.

Animals↗
PubMed1980

Interaction between phencyclidine (PCP) and GABA-ergic drugs: clinical implications.

Pretreatment (IP) of mice with (-) baclofen, muscimol, 4,5,6,7-tetrahydroisoxazolo (S,4-c) pyridin-3-ol hydrate (THIP), aminooxyacetic acid (AOAA) or gamma-acetylenic GABA caused a dose-dependent inhibition of thelocomotor stimulant effect of phencyclidine (PCP, 8 mg/kg). Although (-) baclofen was found to be the most effective PCP antagonist, its (+) isomer was inactive. The maximum blocking effect of AOAA was seen in animals treated 3 and 6 hr earlier. Except for gamma-acetylenic GABA, none of these drugs significantly blocked the locomotor stimulant effect of d-amphetamine (3 mg/kg, IP). Diazepam reduced d-amphetamine response, but failed to influence PCP-induced stimulation. The locomotor stimulant effect of PCP, unlike that of d-amphetamine, may be the result of a specific GABA antagonistic effect at certain dopamine-rich areas of the brain. It seems that (-) baclofen may prove to be useful in the management of PCP intoxication. Administration of higher doses of PCP (20 and 50 mg/kg) in mice pretreated with (-) baclofen resulted in the development of surgical anesthesia manifested as the loss of a) righting reflex, b) pain sensation and c) corneal reflex. The duration of the general anesthetic response was found to be a function of the doses of both (-) baclofen and PCP. The possible use of (-) baclofen as an adjuvant to general anesthetic is discussed.

Aminooxyacetic Acid↗
PubMed1979

Hypothermic effects of apomorphine homologues in mice.

A single intraperitoneal (i.p.) injection in mice of apomorphine (I) and its analogues norapomorphine (II), N-ethylnorapomorphine (III), N-n-propylnorapomorphine (IV) and apocodeine (V), caused dose-related decreases in deep-core body temperature. The neuroleptic agent haloperidol blocked the hypothermia produced by these apomorphines but alpha-methyl-p-tyrosine failed to do so. This indicated a direct post-synaptic stimulation of dopamine receptors. Methysergide potentiated the hypothermic effect of the apomorphine analogues. Taking the amount of apomorphine to produce a 3 degree C fall in temperature at 30 min as unity, the approximate relative potencies were: I 1.00, II 0.06, III 47.50, IV 85.00, V 0.340. The doses of the apomorphines needed to produce hypothermia were much less than those needed to cause stereotypy. The ratios of the minimal doses required to produce hypothermia, to those producing stereotypy were: I 8.82, II 4.00, III 125.00, IV 28.50, V 1.43.

Animals↗
PubMed1978

Comparison of the dopaminergic effects of apomorphine and (-)-N-n-propylnorapomorphine.

(-)-N-n-propylnorapomorphine (NPA) was found to be 2.3 times more active than apomorphine in producing stereotypy in novice mice. This potency ratio was not changed by reserpine pretreatment (4 h prior). However, when mice pretreated with reserpine 24 h earlier were used, NPA was found to be 6.5 times more active in producing locomotor stimulation and 8.7 times more active in producing stereotypy than apomorphine. In these mice, a second dose of reserpine or alpha-methyl-p-tyrosine (alphaMT) given 4 h prior to NPA administration considerably reduced the locomotor effects of NPA. Such treatments did not modify the effects of apomorphine. Phenoxybenzamine failed to alter the responses of both these drugs. It was concluded that, while apomorphine possesses direct dopamine (DA) receptor stimulant effect, that of NPA is partly direct and partly indirect in nature. In novice mice, NPA was 91 times more active than apomorphine in inhibiting the alphaMT-induced depletion of brain DA. The question is raised why the powerful DA receptor agonistic effect of NPA did not produce equivalent behavioral responses in mice. The likely explanation would be that, in addition to its effect on the striatonigral DA system from which the stereotypic response originates, NPA also exerts a predominant effect on the mesolimbic areas. The combined effect of NPA on these two components of the DA system is reflected in the biochemical results. The overall dopaminergic effect of NPA is several times greater than that of apomorphine.

Animals↗