Grayanotoxin I

370.48

412.52

26711

CRYSTALS FROM ETHYL ACETATE

127

0.73910

1.32 g/cm3

258-260 °C

549.3ºC at 760 mmHg

184.3ºC

1.593

SOL IN HOT WATER, ALCOHOL, ACETIC ACID, HOT CHLOROFORM; VERY SLIGHTLY SOL IN BENZENE, ETHER, PETROLEUM ETHER

Peritoneal-mouse LD50; 1.31 mg/kg; subcutaneous-mouse LD50: 0.148 mg/kg

Flammable; burning produces irritating fumes

D25 -8.8° (c = 2.3 in ethanol)

I

6.1(a)

3172

Warehouse ventilated, low temperature and dry

THE PHARMACOLOGICAL MECHANISM OF ACTION OF GRAYANOTOXIN I ON NERVE AXON, SKELETAL & CARDIAC MUSCLES IS REVIEWED.[FUKUDA H, ONO H; GRAYANOTOXINS; IGAKU NO AYUMI 112(13) 954 (1980)]

most toxic

PHENYTOIN ANTAGONIZED THE INOTROPIC EFFECT OF GRAYANOTOXIN I ON ISOLATED GUINEA PIG ATRIA, PROBABLY ACTING AS AN INHIBITOR OF THE SODIUM INFLUX ACROSS THE CELL MEMBRANE.|ACETYLANDROMEDOL (10-40 MUG/KG) INJECTED IV INTO ANESTHETIZED CATS INCREASED CENTRAL NERVOUS SYMPATHETIC ACTIVITY WHICH LASTED LESS THAN 1 HR. CLONIDINE HCL DECREASED THE SYMPATHETIC ACTIVITY.

TOXIC DITERPENOIDS PRESENT IN LEAVES OF VARIOUS SPECIES OF RHODODENDRON...& LEUCOTHOE, ERICACEAE; ALSO FOUND IN HONEY FROM RHODODENDRON FLOWERS. THIRTEEN GRAYANOTOXINS HAVE BEEN ISOLATED... ISOLATION OF GRAYANOTOXINS I, II, III: KAKISAWA ET AL, TETRAHEDRON 21, 3091 (1965)... FROM LEUCOTHOE GRAYANA MAX, ERICACEAE: MIYAJIMI, TAKEI, J AGR CHEM SOC JAPAN 10, 1093 (1934); FROM RHODODENDRON MAXIMUM L, ERICACEAE: WOOD ET AL, J AM CHEM SOC 76, 5689 (1954).

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)|Drugs that interrupt transmission at the skeletal neuromuscular junction by causing sustained depolarization of the motor end plate. These agents are primarily used as adjuvants in surgical anesthesia to cause skeletal muscle relaxation. (See all compounds classified as Neuromuscular Depolarizing Agents.)

GRAYANOTOXIN INHIBITED THE INITIATION OF ACTION POTENTIALS OF RAT SOLEUS & EXTENSOR DIGITORUM LONGUS MUSCLES BY REDUCING THE RESTING POTENTIAL & INCREASING THE CRITICAL FIRING LEVEL. THE DECREASE IN RESTING POTENTIAL INDUCED BY THIS TOXIN WAS ASSOCIATED WITH REDUCTION OF THE EFFECTIVE MEMBRANE RESISTANCE. THESE PHENOMENA WERE NOT OBSERVED ON WITHDRAWAL OF SODIUM FROM THE MEDIUM; THEREFORE, DEPOLARIZATION OF THE MEMBRANE IN THE TOXIC SOLN IS APPARENTLY DUE TO INCREASED PERMEABILITY OF THE MEMBRANE TO SODIUM IONS.|THE ACTION OF GRAYANOTOXIN I IN MODIFYING THE KINETICS OF THE NA CHANNEL GATING MECHANISM WAS STUDIED WITH VOLTAGE CLAMPED, INTERNALLY PERFUSED SQUID GIANT AXONS. A KINETIC MODEL IS PROPOSED TO ACCOUNT FOR THE GRAYANOTOXIN MODULATION OF THE NA CHANNEL. THE GRAYANOTOXIN I MOLECULE BINDS TO THE NA CHANNEL IN ITS CLOSED & OPEN CONFORMATIONS TO YIELD A MODIFIED OPEN CHANNEL WHICH UNDERGOES A SLOW OPENING.|GRAYANOTOXIN I PRODUCED A SLIGHT DEPOLARIZATION AND APPEARS TO DECREASE THE UPSTROKE VELOCITY OF THE ACTION POTENTIAL, WITH CONCOMITANT INCREASES IN ISOMETRIC CONTRACTILE FORCE IN PRESENCE OR ABSENCE OF PROPRANOLOL. POSITIVE INOTROPIC & ARRHYTHMIC EFFECTS WERE REVERSIBLE AFTER THE WASHOUT OF THE DRUG.|RELATIONSHIP BETWEEN CHEMICAL STRUCTURE, POSITIVE INOTROPIC POTENCY & LETHAL DOSE OF GRAYANOTOXINS & RELATED COMPOUNDS WAS STUDIED FOLLOWING IV ADMIN TO GUINEA PIGS. THE POSITIVE INOTROPIC EFFECT (PIE) WAS EXAM IN PAPILLARY MUSCLE ISOLATED FROM THE HEART. GRAYANOTOXIN I WAS USED AS A STD IN THIS STUDY. THE STUDY CLARIFIED THE CONTRIBUTION OF FUNCTIONAL GROUPS IN THE MOLECULES; THE PRESENCE OF 3BETA-HYDROXYL & 10BETA-METHYL GROUPS ATTACHED TO THE GRAYANANE SKELETON IS ESSENTIAL FOR THE DEVELOPMENT OF PIE. LD50 VALUES OF 10 COMPOUNDS INCL GRAYANOTOXIN I BORE A SIGNIFICANT CORRELATION (R= 0.68, P LESS THAN 0.05).

acetylandromedol

CHARACTERIZATION OF DITERPENES OF THE GRAYANOTOXIN TYPE WAS BY THIN-LAYER CHROMATOGRAPHY & SPECTROSCOPY.